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Chodur GM, Steinberg FM. Human MicroRNAs Modulated by Diet: A Scoping Review. Adv Nutr 2024; 15:100241. [PMID: 38734078 PMCID: PMC11150912 DOI: 10.1016/j.advnut.2024.100241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 05/04/2024] [Accepted: 05/08/2024] [Indexed: 05/13/2024] Open
Abstract
Because of their role in regulating and fine-tuning gene expression in the posttranscriptional period, microRNA (miRNA) may represent a mediating factor that connects diet and metabolic regulation. Given the vast number of miRNAs and that modulations in miRNA happen in response to a variety of stimuli, a comprehensive registry of miRNAs impacted by diet and the food items that modulate them, would have utility in the identification of miRNA complements for analysis of diet interventions and in helping to establish linkages between the specific impacts of diet components. A scoping literature search of online databases (PubMed, SCOPUS, EMBASE, and Web of Science) was performed. Only studies in human populations, those that used a diet intervention or meal challenge, and those that measured miRNA profiles in the same subject at multiple time points were included. Of the 6167 studies screened, only 25 met the study criteria and were included in the review. Seven studies examined miRNA following a meal challenge, whereas 18 investigated miRNA following a sustained diet intervention. The results demonstrated that miRNA are modulated following a variety of diet interventions and that intensity of miRNA response is greater in metabolically healthy subjects. Heterogeneity in the intensity and length of the diet intervention, the study populations being observed, and the methodology through which target miRNA are identified contribute to a lack of comparability across studies. The findings of this review highlight the need for more study of miRNA responsiveness to intake and provide recommendations for future research.
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Affiliation(s)
- Gwen M Chodur
- Department of Nutrition, University of California-Davis, Davis, CA, United States
| | - Francene M Steinberg
- Department of Nutrition, University of California-Davis, Davis, CA, United States.
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Uzair M, Haq TU, Ali S, Hussain M, Jalil F, Ali Y, Shah AA. The miRNA variants MIR196A2 (rs11614913) and MIR423 (rs6505162) contribute to an increase in the risk of myocardial infarction. Mol Genet Genomic Med 2024; 12:e2323. [PMID: 38013659 PMCID: PMC10767615 DOI: 10.1002/mgg3.2323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/26/2023] [Accepted: 11/10/2023] [Indexed: 11/29/2023] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) are small, single-stranded RNA molecules that negatively regulate gene expression and play a key role in the pathogenesis of human diseases. Recent studies have suggested that miRNAs contribute to cardiovascular diseases (CVDs). However, the association between single-nucleotide polymorphisms (SNPs) in miRNAs and myocardial infarction (MI) remains in infancy. AIM The current study was designed to find out the association of SNPs in MIR196A2 and MIR423 (rs11614913 and rs6505162, respectively). METHODS Using Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS PCR) in 400 cases (MI patients) and 336 healthy controls. Using different inheritance models (co-dominant, homozygous dominant, homozygous recessive, and additive models), the association of these SNPs was genotyped with MI risk. RESULTS For variant rs11614913, significant distribution of the genotypes among the cases and controls was determined by co-dominant [χ2 = 29.19, 2; p value < 0.0001], dominant (C/C vs. C/T + T/T) [OR = 0.45 (0.34 to 0.61); p < 0.0001], recessive (T/T vs. C/T + C/C) [OR = 1.009 (0.63 to 1.63); p-value p value > 0.999], and additive models [OR = 0.65 (0.52 to 0.80); p value = 0.0001]. Similarly, a significant association of rs6505162 was determined by co-dominant [χ2 = 24.29, 2; p value < 0.0001], dominant (C/C vs. A/C+ A/A) [OR = 0.44 (0.32 to 0.61); p value < 0.0001], recessive (A/A vs. A/C + C/C) [OR = 1.29 (0.85 to 1.98); p value = 0.28], and additive models [OR = 0.65 (0.52 to 0.81); p value = 0.0001]. CONCLUSION Therefore, the current study showed that both variants rs11614913 and rs6505162 are significantly associated with MI in the Pakistani population.
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Affiliation(s)
- Muhammad Uzair
- Department of Biotechnology, Faculty of Biological SciencesUniversity of MalakandChakdaraPakistan
| | - Taqweem Ul Haq
- Department of Biotechnology, Faculty of Biological SciencesUniversity of MalakandChakdaraPakistan
| | - Sajjad Ali
- Department of Biotechnology, Faculty of Biological SciencesUniversity of MalakandChakdaraPakistan
| | - Manzar Hussain
- Department of Biotechnology, Faculty of Biological SciencesUniversity of MalakandChakdaraPakistan
| | - Fazal Jalil
- Department of BiotechnologyAbdul Wali Khan University Mardan (AWKUM)MardanPakistan
| | - Yasir Ali
- School of Biomedical SciencesThe Chinese University of Hong KongHong KongHong Kong
| | - Aftab Ali Shah
- Department of Biotechnology, Faculty of Biological SciencesUniversity of MalakandChakdaraPakistan
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Goncalves BDS, Meadows A, Pereira DG, Puri R, Pillai SS. Insight into the Inter-Organ Crosstalk and Prognostic Role of Liver-Derived MicroRNAs in Metabolic Disease Progression. Biomedicines 2023; 11:1597. [PMID: 37371692 PMCID: PMC10295788 DOI: 10.3390/biomedicines11061597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/19/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Dysfunctional hepatic metabolism has been linked to numerous diseases, including non-alcoholic fatty liver disease, the most common chronic liver disorder worldwide, which can progress to hepatic fibrosis, and is closely associated with insulin resistance and cardiovascular diseases. In addition, the liver secretes a wide array of metabolites, biomolecules, and microRNAs (miRNAs) and many of these secreted factors exert significant effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the involvement of liver-derived miRNAs in biological processes with an emphasis on delineating the communication between the liver and other tissues associated with metabolic disease progression. Furthermore, the review identifies the primary molecular targets by which miRNAs act. These consolidated findings from numerous studies provide insight into the underlying mechanism of various metabolic disease progression and suggest the possibility of using circulatory miRNAs as prognostic predictors and therapeutic targets for improving clinical intervention strategies.
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Affiliation(s)
- Bruno de Souza Goncalves
- Department of Surgery and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Avery Meadows
- Department of Surgery and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Duane G Pereira
- Department of Surgery and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Raghav Puri
- Department of Surgery and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Sneha S Pillai
- Department of Surgery and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
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Chaudhari U, Pohjolainen L, Ruskoaho H, Talman V. Genome-wide profiling of miRNA-gene regulatory networks in mouse postnatal heart development-implications for cardiac regeneration. Front Cardiovasc Med 2023; 10:1148618. [PMID: 37283582 PMCID: PMC10241105 DOI: 10.3389/fcvm.2023.1148618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/02/2023] [Indexed: 06/08/2023] Open
Abstract
Background After birth, mammalian cardiomyocytes substantially lose proliferative capacity with a concomitant switch from glycolytic to oxidative mitochondrial energy metabolism. Micro-RNAs (miRNAs) regulate gene expression and thus control various cellular processes. Their roles in the postnatal loss of cardiac regeneration are however still largely unclear. Here, we aimed to identify miRNA-gene regulatory networks in the neonatal heart to uncover role of miRNAs in regulation of cell cycle and metabolism. Methods and results We performed global miRNA expression profiling using total RNA extracted from mouse ventricular tissue samples collected on postnatal day 1 (P01), P04, P09, and P23. We used the miRWalk database to predict the potential target genes of differentially expressed miRNAs and our previously published mRNA transcriptomics data to identify verified target genes that showed a concomitant differential expression in the neonatal heart. We then analyzed the biological functions of the identified miRNA-gene regulatory networks using enriched Gene Ontology (GO) and KEGG pathway analyses. Altogether 46 miRNAs were differentially expressed in the distinct stages of neonatal heart development. For twenty miRNAs, up- or downregulation took place within the first 9 postnatal days thus correlating temporally with the loss of cardiac regeneration. Importantly, for several miRNAs, including miR-150-5p, miR-484, and miR-210-3p there are no previous reports about their role in cardiac development or disease. The miRNA-gene regulatory networks of upregulated miRNAs negatively regulated biological processes and KEGG pathways related to cell proliferation, while downregulated miRNAs positively regulated biological processes and KEGG pathways associated with activation of mitochondrial metabolism and developmental hypertrophic growth. Conclusion This study reports miRNAs and miRNA-gene regulatory networks with no previously described role in cardiac development or disease. These findings may help in elucidating regulatory mechanism of cardiac regeneration and in the development of regenerative therapies.
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Liao Q, Ye Y, Li Z, Chen H, Zhuo L. Prediction of miRNA-disease associations in microbes based on graph convolutional networks and autoencoders. Front Microbiol 2023; 14:1170559. [PMID: 37187536 PMCID: PMC10175670 DOI: 10.3389/fmicb.2023.1170559] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 03/21/2023] [Indexed: 05/17/2023] Open
Abstract
MicroRNAs (miRNAs) are short RNA molecular fragments that regulate gene expression by targeting and inhibiting the expression of specific RNAs. Due to the fact that microRNAs affect many diseases in microbial ecology, it is necessary to predict microRNAs' association with diseases at the microbial level. To this end, we propose a novel model, termed as GCNA-MDA, where dual-autoencoder and graph convolutional network (GCN) are integrated to predict miRNA-disease association. The proposed method leverages autoencoders to extract robust representations of miRNAs and diseases and meantime exploits GCN to capture the topological information of miRNA-disease networks. To alleviate the impact of insufficient information for the original data, the association similarity and feature similarity data are combined to calculate a more complete initial basic vector of nodes. The experimental results on the benchmark datasets demonstrate that compared with the existing representative methods, the proposed method has achieved the superior performance and its precision reaches up to 0.8982. These results demonstrate that the proposed method can serve as a tool for exploring miRNA-disease associations in microbial environments.
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Affiliation(s)
- Qingquan Liao
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Yuxiang Ye
- School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, China
| | - Zihang Li
- School of Computing and Data Science, Xiamen University Malaysia, Sepang, Selangor, Malaysia
| | - Hao Chen
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
- *Correspondence: Hao Chen
| | - Linlin Zhuo
- School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, China
- Linlin Zhuo
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Abdel Rhman M, Owira P. The role of microRNAs in the pathophysiology, diagnosis, and treatment of diabetic cardiomyopathy. J Pharm Pharmacol 2022; 74:1663-1676. [PMID: 36130185 DOI: 10.1093/jpp/rgac066] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 08/23/2022] [Indexed: 11/13/2022]
Abstract
INTRODUCTION Diabetic cardiomyopathy (DCM) is an end-point macrovascular complication associated with increased morbidity and mortality in 12% of diabetic patients. MicroRNAs (miRNAs) are small noncoding RNAs that can act as cardioprotective or cardiotoxic agents in DCM. METHODS We used PubMed as a search engine to collect and analyse data in published articles on the role of miRNAs on the pathophysiology, diagnosis and treatment of DCM. RESULTS MiRNAs play an essential role in the pathophysiology, diagnosis and treatment of DCM due to their distinct gene expression patterns in diabetic patients compared to healthy individuals. Advances in gene therapy have led to the discovery of potential circulating miRNAs, which can be used as biomarkers for DCM diagnosis and prognosis. Furthermore, targeted miRNA therapies in preclinical and clinical studies, such as using miRNA mimics and anti-miRNAs, have yielded promising results. Application of miRNA mimics and anti-miRNAs via different nanodrug delivery systems alleviate hypertrophy, fibrosis, oxidative stress and apoptosis of cardiomyocytes. CONCLUSION MiRNAs serve as attractive potential targets for DCM diagnosis, prognosis and treatment due to their distinctive expression profile in DCM development.
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Affiliation(s)
- Mahasin Abdel Rhman
- Department of Pharmacology, Discipline of Pharmaceutical Sciences, Molecular and Clinical Pharmacology Research Laboratory, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Peter Owira
- Department of Pharmacology, Discipline of Pharmaceutical Sciences, Molecular and Clinical Pharmacology Research Laboratory, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
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Yao C, Ren J, Huang R, Tang C, Cheng Y, Lv Z, Kong L, Fang S, Tao J, Fu Y, Zhu Q, Fang M. Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway. J Neuroinflammation 2022; 19:211. [PMID: 36045396 PMCID: PMC9434879 DOI: 10.1186/s12974-022-02568-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT. METHODS We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats. RESULTS Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects. CONCLUSIONS In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.
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Affiliation(s)
- Chongjie Yao
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 People’s Republic of China
| | - Jun Ren
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Ruixin Huang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Cheng Tang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Yanbin Cheng
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Zhizhen Lv
- The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053 People’s Republic of China
| | - Lingjun Kong
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Sitong Fang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Jiming Tao
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Yangyang Fu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Qingguang Zhu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
| | - Min Fang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200437 People’s Republic of China
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 People’s Republic of China
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van den Homberg DAL, van der Kwast RVCT, Quax PHA, Nossent AY. N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4. Int J Mol Sci 2022; 23:1057. [PMID: 35162982 PMCID: PMC8835077 DOI: 10.3390/ijms23031057] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 01/10/2022] [Accepted: 01/17/2022] [Indexed: 12/13/2022] Open
Abstract
N-6-methyladenosine (m6A) is the most prevalent post-transcriptional RNA modification in eukaryotic cells. The modification is reversible and can be dynamically regulated by writer and eraser enzymes. Alteration in the levels of these enzymes can lead to changes in mRNA stability, alternative splicing or microRNA processing, depending on the m6A-binding proteins. Dynamic regulation of mRNA m6A methylation after ischemia and hypoxia influences mRNA stability, alternative splicing and translation, contributing to heart failure. In this study, we studied vasoactive microRNA m6A methylation in fibroblasts and examined the effect of hypoxia on microRNAs methylation using m6A immunoprecipitation. Of the 19 microRNAs investigated, at least 16 contained m6A in both primary human fibroblasts and a human fibroblast cell line, suggesting vasoactive microRNAs are commonly m6A methylated in fibroblasts. More importantly, we found that mature microRNA m6A levels increased upon subjecting cells to hypoxia. By silencing different m6A writer and eraser enzymes followed by m6A immunoprecipitation, we identified METTL4, an snRNA m6A methyltransferase, to be predominantly responsible for the increase in m6A modification. Moreover, by using m6A-methylated microRNA mimics, we found that microRNA m6A directly affects downstream target mRNA repression efficacy. Our findings highlight the regulatory potential of the emerging field of microRNA modifications.
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Affiliation(s)
- Daphne A. L. van den Homberg
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (D.A.L.v.d.H.); (R.V.C.T.v.d.K.); (P.H.A.Q.)
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
| | - Reginald V. C. T. van der Kwast
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (D.A.L.v.d.H.); (R.V.C.T.v.d.K.); (P.H.A.Q.)
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
| | - Paul H. A. Quax
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (D.A.L.v.d.H.); (R.V.C.T.v.d.K.); (P.H.A.Q.)
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
| | - A. Yaël Nossent
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (D.A.L.v.d.H.); (R.V.C.T.v.d.K.); (P.H.A.Q.)
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- Department for Laboratory Medicine, Medical University of Vienna, AT-1090 Vienna, Austria
- Department of Internal Medicine II, Medical University of Vienna, AT-1090 Vienna, Austria
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Wang J, Xu L, Tian L, Sun Q. Circulating microRNA-208 family as early diagnostic biomarkers for acute myocardial infarction: A meta-analysis. Medicine (Baltimore) 2021; 100:e27779. [PMID: 34941030 PMCID: PMC8702233 DOI: 10.1097/md.0000000000027779] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 10/28/2021] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE Many recent studies have demonstrated that serum miRNA-208 (miR-208) could be a powerful biomarker in the early diagnosis of acute myocardial infarction (AMI). However, the result of previous studies was not accurate due to the small sample sizes and controversial issues. Therefore, this study was performed to investigate the relationship between the expression levels of miR-208 and AMI. MATERIALS AND METHODS According to the inclusion and exclusion criteria, a preliminary literature search was performed. The study was based on articles published in PubMed, Embase, Cochrane databases before September 30, 2019. Two staff members extracted data from the included articles for meta-analysis. These data were analyzed for sensitivity, specificity, diagnostic odds ratio, and summary receiver operator curve (SROC) analyses. RESULTS This study included 13 pieces of literature, which contains 1703 patients with AMI and 1589 controls. The main results of our meta-analysis were as follows: The pool sensitivity and specificity of miR-208 for diagnosing AMI was 83% and 97%. The area under the SROC curve (AUC) was 93%. Mir-208 had a highly effective diagnostic capacity to distinguish AMI from chest pain patients with an AUC of 93%. CONCLUSIONS The results showed that circulating miR-208 was a reliable biomarker both for diagnosting ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). MiR-208 was sufficient to distinguish AMI patients with chest pain from healthy controls.
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The effect of eight weeks of moderate and high intensity aerobic training on the gene expression of Mir-145, Wnt3a and Dab2 in the heart tissue of type 2 diabetic rats. J Diabetes Metab Disord 2021; 20:1597-1604. [PMID: 34900811 DOI: 10.1007/s40200-021-00909-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/25/2021] [Indexed: 10/20/2022]
Abstract
Purpose Pathological hypertrophy of heart tissue has been attributed to changes in some microRNAs and their target genes in heart tissue. This study intended to study the effects of eight weeks of moderate and high intensity aerobic training (MIT&HIT) on the mRNA of Mir-145, Wnt3a, and Dab2 in heart tissue of type 2 diabetic rats. Methods To implement this experimental research, 60 male Wistar rats were randomly divided into 6 groups, including Healthy-control (HC), Diabetic-control (DC), Moderate intensity training (MIT), Diabetes-MIT (DMIT), high intensity training (HIT) and Diabetes-HIT (DHIT). The aerobic training was conducted with moderate (50-60% VO2max) and high (85-90% VO2max) intensity, 5 days a week, for 8 weeks. The Mir-145, Wnt3a and Dab2 gene expression in the heart tissue samples was measured by Real Time PCR. Data were analyzed by one-way ANOVA and Tukey post hoc test at the P < 0.05. Results Moderate and high intensity aerobic training was associated with non-significant increase in Mir-145 mRNA of Heart tissue in type 2 diabetic rats than the diabetic control group(P < 0.05). Moderate and high intensity aerobic training was associated with significant increase in Wnt3a mRNA (P = 0.001) and significant decrease in Dab-2 mRNA (P = 0.001) of Heart tissue in type 2 diabetic rats than the diabetic control group. The Dab-2 mRNA was significantly lower of heart tissue in the diabetes- high intensity training group than the diabetes- moderate intensity training group (P = 0.001). Conclusion It seems that moderate and high intensity aerobic exercise can help regulate the genes of the physiological hypertrophy pathway of the heart tissue in diabetes.
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MicroRNA miR-215-5p regulates doxorubicin-induced cardiomyocyte injury by targeting ZEB2. J Cardiovasc Pharmacol 2021; 78:622-629. [PMID: 34282068 DOI: 10.1097/fjc.0000000000001110] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/21/2021] [Indexed: 11/26/2022]
Abstract
ABSTRACT Doxorubicin (DOX) is a chemotherapeutic drug for treating various cancers. However, the DOX-induced cardiotoxicity greatly limits its clinical application. MicroRNAs (miRNAs) are emerged as critical mediators of cardiomyocyte injury. This work explored the function of miR-215-5p in the regulation of DOX-induced mouse HL-1 cardiomyocyte injury. An in vitro model of DOX-treated cardiotoxicity was established in HL-1 cells. Gene expression was measured by RT-qPCR. Cell viability was detected using CCK-8. Cell death and apoptosis were tested using TUNEL, flow cytometry, and caspase 3/7 activity assays. Luciferase reporter assay was used to examine the target of miR-215-5p. We found that DOX induced cardiomyocyte injury and upregulated miR-215-5p in HL-1 cells. Inhibition of miR-215-5p attenuated DOX-induced cardiomyocyte death and apoptosis in vitro. Mechanistical experiments indicated that ZEB2 was targeted by miR-215-5p. Additionally, ZEB2 expression was reduced in DOX-treated HL-1 cells. Rescue assays indicated that ZEB2 knockdown reversed the effects of miR-215-5p inhibition. In conclusion, miR-215-5p inhibition protects HL-1 cells against DOX-induced injury by upregulating ZEB2 expression.
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ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis. Cells 2021; 10:cells10061512. [PMID: 34208452 PMCID: PMC8235602 DOI: 10.3390/cells10061512] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. Method: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. Results: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. Conclusion: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.
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Recent Highlights of Research on miRNAs as Early Potential Biomarkers for Cardiovascular Complications of Type 2 Diabetes Mellitus. Int J Mol Sci 2021; 22:ijms22063153. [PMID: 33808800 PMCID: PMC8003798 DOI: 10.3390/ijms22063153] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/12/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) and its complications pose a serious threat to the life and health of patients around the world. The most dangerous complications of this disease are vascular complications. Microvascular complications of T2DM include retinopathy, nephropathy, and neuropathy. In turn, macrovascular complications include coronary artery disease, peripheral artery disease, and cerebrovascular disease. The currently used diagnostic methods do not ensure detection of the disease at an early stage, and they also do not predict the risk of developing specific complications. MicroRNAs (miRNAs) are small, endogenous, noncoding molecules that are involved in key processes, such as cell proliferation, differentiation, and apoptosis. Recent research has assigned them an important role as potential biomarkers for detecting complications related to diabetes. We suggest that utilizing miRNAs can be a routine approach for early diagnosis and prognosis of diseases and may enable the development of better therapeutic approaches. In this paper, we conduct a review of the latest reports demonstrating the usefulness of miRNAs as biomarkers in the vascular complications of T2DM.
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The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B. Biosci Rep 2021; 40:221736. [PMID: 31894853 PMCID: PMC6970065 DOI: 10.1042/bsr20191000] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 12/03/2019] [Accepted: 12/17/2019] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.
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Protective Effect of miR-204 on Doxorubicin-Induced Cardiomyocyte Injury via HMGB1. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8819771. [PMID: 33274007 PMCID: PMC7695502 DOI: 10.1155/2020/8819771] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/24/2020] [Accepted: 11/07/2020] [Indexed: 12/22/2022]
Abstract
The toxicity of doxorubicin (DOX) limits its clinical application. Nevertheless, at present, there is no effective drug to prevent DOX-induced cardiac injury. miR-204 is a newly discovered miRNA with many protective effects on cardiovascular diseases. However, little research has been done on the effects of miR-204 on DOX-induced cardiac injury. Our study is aimed at investigating the effect of miR-204 on DOX-induced myocardial injury. An adenoassociated virus system was used to achieve cardiac-specific overexpression of miR-204. Two weeks later, the mice were intraperitoneally injected with DOX (15 mg/kg) to induce cardiac injury. H9c2 myocardial cells were used to validate the role of miR-204 in vitro. Our study showed that miR-204 expression was decreased in DOX-treated hearts. miR-204 overexpression improved cardiac function and alleviated cardiac inflammation, apoptosis, and autophagy induced by DOX. In addition, our results showed that miR-204 prevented DOX-induced injury in cardiomyocytes by directly decreasing HMGB1 expression. Moreover, the overexpression of HMGB1 could offset the protective effects of miR-204 against DOX-induced cardiac injury. In summary, our study showed that miR-204 protected against DOX-induced cardiac injury via the inhibition of HMGB1, and increasing miR-204 expression may be a new treatment option for patients with DOX-induced cardiac injury.
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Zhou F, Liu Z, Cai H, Miao Z, Wei F, Song C. Role of microRNA-15a-5p/TNFAIP3-interacting protein 2 axis in acute lung injury induced by traumatic hemorrhagic shock. Exp Ther Med 2020; 20:2. [PMID: 32934667 PMCID: PMC7471858 DOI: 10.3892/etm.2020.9130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 06/17/2020] [Indexed: 12/15/2022] Open
Abstract
The present study aimed to investigate the role of microRNA (miR)-15a-5p in the pathogenesis of acute lung injury induced by traumatic hemorrhagic shock (THS), and to explore the underlying molecular mechanism. The expression level of miR-15a-5p was detected using reverse transcription-quantitative (RT-qPCR) and the association between miR-15a-5p and TNFAIP3-interacting protein 2 (TNIP2) was revealed using TargetScan and dual luciferase reporter assays. To investigate the effect of miR-15a-5p on THS-induced acute lung injury, a THS rat model was established. Lung capillary permeability and lung edema were then determined. Moreover, proinflammatory factors in the bronchoalveolar lavage fluid (BALF) and serum of the THS rat model were detected using ELISA. In addition, protein levels in the current study were measured via western blotting. It was revealed that miR-15a-5p was significantly upregulated in both patients with THS and samples from the THS rat model. TNIP2 represents a direct target of miR-15a-5p, and it was downregulated in both patients with THS and the THS rat model. Further analyses indicated that downregulation of miR-15a-5p significantly relieved acute lung injury induced by THS, evidenced by a decreased ratio of Evan's blue dye (EBD) in the BALF to EBD in plasma of THS rats, decreased lung permeability index and reduced lung wet/dry ratio. Inhibition of miR-15a-5p also decreased THS-induced upregulation of pro-inflammatory factors. Furthermore, the data revealed that THS-induced NF-κB activation in the lung tissues of rats was inhibited by miR-15a-5p knockdown. Moreover, it was demonstrated that all the effects of miR-15a-5p on THS rats were ablated following TNIP2 silencing. Taken together, the data of the current study indicate that miR-15a-5p downregulation serves a protective role in THS-induced acute lung injury via directly targeting TNIP2.
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Affiliation(s)
- Feng Zhou
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
| | - Zhizhen Liu
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
| | - Huazhong Cai
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
| | - Zhenjun Miao
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
| | - Faxing Wei
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
| | - Chao Song
- Department of Emergency, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
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17
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Ding Y, Wang Y, Zhang W, Jia Q, Wang X, Li Y, Lv S, Zhang J. Roles of Biomarkers in Myocardial Fibrosis. Aging Dis 2020; 11:1157-1174. [PMID: 33014530 PMCID: PMC7505259 DOI: 10.14336/ad.2020.0604] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 06/04/2020] [Indexed: 12/13/2022] Open
Abstract
Myocardial fibrosis is observed in various cardiovascular diseases and plays a key role in the impairment of cardiac function. Endomyocardial biopsy, as the gold standard for the diagnosis of myocardial fibrosis, has limitations in terms of clinical application. Therefore, biomarkers have been recommended for noninvasive assessment of myocardial fibrosis. This review discusses the role of biomarkers in myocardial fibrosis from the perspective of collagen.
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Affiliation(s)
- Yuejia Ding
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Yuan Wang
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Wanqin Zhang
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Qiujin Jia
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
| | - Xiaoling Wang
- 3Qian'an Hospital of Traditional Chinese Medicine, Qian'an 064400, China
| | - Yanyang Li
- 4Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Shichao Lv
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.,2Tianjin Key Laboratory of Traditional Research of TCM Prescription and Syndrome, Tianjin 300000, China
| | - Junping Zhang
- 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
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18
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The inhibition of tumor protein p53 by microRNA-151a-3p induced cell proliferation, migration and invasion in nasopharyngeal carcinoma. Biosci Rep 2020; 39:220889. [PMID: 31652456 PMCID: PMC6822577 DOI: 10.1042/bsr20191357] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 09/05/2019] [Accepted: 09/13/2019] [Indexed: 02/06/2023] Open
Abstract
A close relation between microRNA-151a-3p (miR-151a-3p) and nasopharyngeal carcinoma (NPC) has been reported, however, the molecular mechanism is still unclear. The aim of the present study was to explore the mechanism in the promotion of miR-151a-3p to NPC progression. The levels of miR-151-3p in several NPC cell lines were detected in order to screen an experimental cell line. MiR-151a-3p mimic and inhibitor were constructed and transfected into 5-8F cells and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). The apoptosis rate, cell migration and invasion were determined by flow cytometry, wound healing and Transwell assays. The predicted target was further verified by luciferase reporter assay. Real-time quantification-PCR and Western blot were carried out for mRNA and protein level analysis. Tumor protein p53 was co-transfected to verify the functions of miR-151a-3p. The miR-151a-3p level in NPC tissues was much higher than that in adjacent tissues. After transfecting cells with miR-151a-3p mimic, the cell proliferation and patients' survival rate were much increased, and this was accompanied by the increase in B-cell lymphoma 2 (Bcl-2) and decreases in Bax and cleaved caspase-3 (P<0.01). Moreover, the migration rate and number of invaded cells were also remarkably increased, however, the miR-151a-3p inhibitor had opposite effects on the 5-8F cells. Noticeably, p53 was revealed as a potential target of miR-151a-3p. Co-transfection of P53 could partially reverse the promotive effects of miR-151a-3p on NPC cell progression. Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.
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Wang X, Tian L, Sun Q. Diagnostic and prognostic value of circulating miRNA-499 and miRNA-22 in acute myocardial infarction. J Clin Lab Anal 2020; 34:2410-2417. [PMID: 32529742 PMCID: PMC7439427 DOI: 10.1002/jcla.23332] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 02/20/2020] [Accepted: 02/22/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Currently, acute myocardial infarction (AMI) represents a serious cardiovascular disease with high morbidity and mortality. Therefore, this study aimed to systematically evaluate the roles of miRNA-499 and miRNA-22 as potential biomarkers for AMI. METHODS According to the inclusion and exclusion criteria, we measured circulating levels of miRNAs in 50 AMI patients and 50 non-MI populations. The expression levels of plasma miRNA-499 and miRNA-22 were analyzed by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). A statistical analysis of clinical data of AMI patients was conducted by 90-day follow-up. RESULTS Real-time PCR analysis showed that the relative expression level of miRNA-499 increased gradually among the three groups (P < .05). However, the expression of miRNA-22 showed a downward trend (P < .05). According to logistic analysis, the relative levels of miRNA-499 and miRNA-22 were important predictors of AMI. When the miRNA-499 and miRNA-22 levels were 0.377 and 0.946 separately, the diagnostic value of miRNA-499 and miRNA-22 for AMI was 86.00% and 86.00% for sensitivity, and 98.00% and 94.00% for specificity, respectively. In addition, compared to the baseline GRACE scoring system, the combination of miRNA-499, miRNA-22, and GRACE scores had a stronger discriminating power for MACE occurrence, with a sensitivity of 100.00% and a specificity of 79.40%. CONCLUSIONS The results showed that plasma miRNA-499 and miRNA-22 were more sensitive and specific for the diagnosis of AMI, suggesting that they can be used as potential biomarkers for clinical diagnosis of AMI.
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Affiliation(s)
- Xiaoqing Wang
- Clinical Laboratory, Hospital Affiliated to Chengde Medical University, Chengde, China
| | - Lu Tian
- Clinical Laboratory, Hospital Affiliated to Chengde Medical University, Chengde, China
| | - Qiyu Sun
- Clinical Laboratory, Hospital Affiliated to Chengde Medical University, Chengde, China
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20
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Ghadrdoost B, Aboutaleb N, Nikougoftar Zarif M, Nakhlestani M, Haghjoo M, Sameie S. Association between cytokines and two circulating micro-RNAs and development of premature ventricular contractions-induced cardiomyopathy. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 22:1125-1131. [PMID: 31998452 PMCID: PMC6885395 DOI: 10.22038/ijbms.2019.36362.8662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Objective(s): Recent progress in understanding the pathogenesis of premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) has suggested a key role for inflammation. The aim of this study was to evaluate the expression of messenger RNAs (mRNAs) and the protein production of interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and interferon-γ (IFN-γ) and two circulating micro-RNAs related to inflammation and cardiovascular disease; miR-155 and miR-146. Materials and Methods: The study population was comprised 25 patients with PIC and 25 patients with normal left ventricular ejection fraction despite frequent PVCs. TNF-α, IL-6, IL10, and IFN-γ levels were evaluated in peripheral blood mononuclear cells (PBMCs) by flow cytometry and their mRNAs were assessed by real time PCR. We analyzed circulating levels of these cytokines by enzyme linked immunosorbent assay (ELISA). Two circulating micro-RNAs, miR-155 and miR-146a, were also investigated. Results: The flow cytometry findings showed that the median fluorescence intensity (MFI) of antibodies reacted with the IL-6 and TNF-α were higher in PIC group than the control group (P-value<0.001). In ELISA, the levels of IL-6 (P-value<0.001) and TNF-α (P-value <0.001) and in RT-PCR the relative expression levels of IL-6 (P-value<0.001) and TNF-α (P-value<0.001) were significantly higher in the PIC group. The relative expression levels of miR-155 and miR-146a were not significantly different between 2 groups (P-value>0.05). Conclusion: In our patients with PIC, there was an elevation in the expression levels of IL-6 and TNF-α in PBMCs. This finding may provide further insights into the inflammatory pathways involved in PIC.
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Affiliation(s)
- Behshid Ghadrdoost
- Physiology Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Aboutaleb
- Physiology Research Center, Physiology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahin Nikougoftar Zarif
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Mojdeh Nakhlestani
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Majid Haghjoo
- Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Shahram Sameie
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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21
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miR32-5p promoted vascular smooth muscle cell calcification by upregulating TNFα in the microenvironment. BMC Immunol 2020; 21:3. [PMID: 31952480 PMCID: PMC6967090 DOI: 10.1186/s12865-019-0324-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 10/22/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Vascular calcification is often associated with chronic inflammation and is a risk factor for brain arterial stiffness. Our previous results showed that miR32-5p was positively correlated with vascular smooth muscle cells (VSMC) calcification, but it is unclear whether miR32-5p promoted VSMC calcification by regulating inflammatory factor production. RESULTS In this study, bioinformatics analysis was used to select tumour necrosis factor α (TNFα) as a candidate inflammatory factor associated with calcification. Moreover, alizarin red staining and qRT-PCR analysis revealed that TNFα produced by BV2 cells was the key promoting factor of VSMC calcification. Interestingly, the expression of TNFα was significantly increased at the mRNA and protein levels after miR32-5p mimic treatment but significantly decreased after miR32-5p antagomir treatment. To explore the mechanism of the regulation of TNFα expression by miR32-5p, bioinformatics analysis indicated that PIKfyve was a candidate target gene of miR32-5p, and luciferase assays verified that the expression of PIKfyve was significantly repressed by miR32-5p mimics. Importantly, rescue experiments showed that the expression of TNFα in BV2 cells treated with miR32-5p antagomir and the PIKfyve inhibitor YM201636 was significantly increased. CONCLUSIONS The production of TNFα in microglia could be affected by miR32-5p targeting PIKfyve, and these results will be beneficial to reveal the mechanism of brain arterial calcification.
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22
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Chen S, Chen H, Yu C, Lu R, Song T, Wang X, Tang W, Gao Y. MiR-638 Repressed Vascular Smooth Muscle Cell Glycolysis by Targeting LDHA. Open Med (Wars) 2019; 14:663-672. [PMID: 31989041 PMCID: PMC6972283 DOI: 10.1515/med-2019-0077] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 07/11/2019] [Indexed: 01/10/2023] Open
Abstract
Background Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) accelerated vascular diseases progression, like atherosclerosis and restenosis. MicroRNAs were reported to participate in modulating diverse cellular processes. Here, we focused on exploring the role of miR-638 in VSMCs glycolysis and underlying mechanism. Methods Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Western blot assay was conducted to determine the expression of cell proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67, as well as Lactate dehydrogenase A (LDHA). VSMCs migration and invasion were evaluated by Transwell assay. Luciferase reporter gene assay and RNA immunoprecipitation were performed to validate the target relationship between miR-638 and LDHA. LDHA and miR-638 expression were also determined. Glycolysis of VSMCs was tested by corresponding Kits. Results Platelet-derived growth factor-bb (PDGF-bb) promoted the VSMCs viability and down-regulated miR-638. Overexpression of miR-638 inhibited cell proliferation, migration and invasion of VSMCs. LDHA was identified as a target of miR-638, and counter-regulated by miR-638. Loss of miR-638 attenuated the suppressor effects on the proliferation, migration and invasion of VSMCs induced by LDHA down-regulation. MiR-638 inhibited the glycolysis of VSMCs by targeting LDHA. Conclusion MiR-638 is down-regulated by PDGF-bb treatment and suppressed the glycolysis of VSMCs via targeting LDHA.
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Affiliation(s)
- Shiyuan Chen
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Hu Chen
- Department of General Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Chaowen Yu
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Ran Lu
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Tao Song
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Xiaogao Wang
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Wenbo Tang
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
| | - Yong Gao
- Department of Vascular Surgery, the First Affiliated Hospital of Bengbu Medical College, Changhuai Road 287, 233003Bengbu City, China
- Tel: +86-133-0965-8851
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Yu D, Wang T, Huang J, Fang X, Fan H, Yi G, Liu Q, Zhang Y, Zeng X, Liu Q. MicroRNA‐9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome. J Cell Biochem 2019; 121:49-62. [DOI: 10.1002/jcb.27830] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 09/14/2018] [Indexed: 12/16/2022]
Affiliation(s)
- Dao‐Rui Yu
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Tao Wang
- Department of nursing humanities, International Nursing School, Hainan Medical University
| | - Jing Huang
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Xing‐Yue Fang
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Hao‐Fei Fan
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Guo‐Hui Yi
- Instrument testing center, Public Research Laboratory, Hainan Medical University
| | - Qiang Liu
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Yu Zhang
- Department of Pharmacology, School of Pharmacy, Nanjing Medical University
| | - Xiang‐Zhou Zeng
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
| | - Qi‐Bing Liu
- Department of Pharmacology School of Basic Medicine and Life Science, Hainan Medical University Haikou China
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Cuesta Torres LF, Zhu W, Öhrling G, Larsson R, Patel M, Wiese CB, Rye KA, Vickers KC, Tabet F. High-density lipoproteins induce miR-223-3p biogenesis and export from myeloid cells: Role of scavenger receptor BI-mediated lipid transfer. Atherosclerosis 2019; 286:20-29. [PMID: 31096070 DOI: 10.1016/j.atherosclerosis.2019.04.227] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 04/17/2019] [Accepted: 04/30/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS We recently showed that miR-223-3p on high-density lipoproteins (HDL) is exported to endothelial cells, where it inhibits inflammation. However, the origin of miR-223-3p on HDL is unknown. We hypothesize that HDL-associated miR-223-3p originates in myeloid cells and is exported to HDL in a scavenger receptor BI (SR-BI)-dependent manner. METHODS Polymorphonuclear neutrophils (PMNs) and human monocyte derived macrophages (HMDMs) were incubated with native HDL (nHDL) or discoidal reconstituted HDL (rHDL). Total RNA was isolated before and after incubation. Mature and primary miR-223-3p (pri-mir-223-3p) levels were quantified by real-time PCR. RESULTS Incubation with nHDL and rHDL increased miR-223-3p export from PMNs and HMDMs. In PMNs, nHDL but not rHDL, increased mature and pri-mir-223-3p. Incubation with HDL also increased Dicer mRNA, a critical regulator of miRNA biogenesis. Incubation of HMDMs with nHDL did not increase cellular levels of mature miR-223-3p, but significantly increased pri-mir-223 levels. Incubation with rHDL had no effect on either mature or pri-mir-223-3p levels. Activated PMNs increased miR-223-3p export to HDL and the production of reactive oxygen species and activated protein kinase C. Blocking HDL binding to SR-BI increased miR-223-3p export to HDL in both PMNs and HMDMs, but did not affect mature and primary miR-223-3p levels. Chemical inhibition of cholesterol flux by Block Lipid Transport (BLT)-1 inhibited HDL-induced pri-mir-223 expression in PMNs. CONCLUSIONS HDL-associated miR-223-3p originates in PMNs and macrophages. HDL stimulates miR-223-3p biogenesis in PMNs in a process that is regulated by SR-BI-mediated lipid flux.
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Affiliation(s)
| | - Wanying Zhu
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Gustav Öhrling
- School of Medical Sciences, University of New South Wales Sydney, NSW, Australia
| | - Rasmus Larsson
- School of Medical Sciences, University of New South Wales Sydney, NSW, Australia
| | - Mili Patel
- School of Medical Sciences, University of New South Wales Sydney, NSW, Australia
| | - Carrie B Wiese
- Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA
| | - Kerry-Anne Rye
- School of Medical Sciences, University of New South Wales Sydney, NSW, Australia
| | - Kasey C Vickers
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA
| | - Fatiha Tabet
- School of Medical Sciences, University of New South Wales Sydney, NSW, Australia.
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25
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Adams V, Linke A. Impact of exercise training on cardiovascular disease and risk. Biochim Biophys Acta Mol Basis Dis 2019; 1865:728-734. [DOI: 10.1016/j.bbadis.2018.08.019] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/03/2018] [Accepted: 08/15/2018] [Indexed: 01/07/2023]
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Wei W, Peng J, Shen T. Rosuvastatin Alleviates Ischemia/Reperfusion Injury in Cardiomyocytes by Downregulating Hsa-miR-24-3p to Target Upregulated Uncoupling Protein 2. Cell Reprogram 2019; 21:99-107. [PMID: 30835496 DOI: 10.1089/cell.2018.0039] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Statins could reduce the risks of coronary heart disease death and ischemic cardiovascular events. In this study, we aim to explore the role of rosuvastatin in ischemia/reperfusion (I/R)-injured cardiomyocytes and the possible mechanism. An I/R model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The protective effects of rosuvastatin pretreatment on OGD/R-injured cardiomyocytes were performed using MTT assay, lactate dehydrogenase (LDH) release assay, and quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics software TargetScan and miRTarBase were used to predict the targeted miRNAs with uncoupling protein (UCP)2. Furthermore, verify the binding capacity of hsa-miR-24-3p and UCP2 with qRT-PCR and dual-luciferase reporter assay. The expression of UCP2, cell viability, LDH level, and apoptosis level affected by downregulated hsa-miR-24-3p were assessed using qRT-PCR, western blotting, MTT, the LDH kit, and flow cytometry. Pretreatment with rosuvastatin could significantly augment cell viability, reduce LDH level, increase the expression of UCP2, and downregulate hsa-miR-24-3p in OGD/R-injured H9c2 cells. miR-24-3p was closely connected with UCP2, and downregulated miR-24-3p could promote UCP2 expression, which presented cell viability increasing, LDH release and cell apoptosis inhibition in OGD/R condition. Moreover, it decreased the protein expression of Cleaved-Caspase-9 and Cyto C. This is the first time our study suggests that rosuvastatin pretreatment protects cardiomyocytes from OGD/R through upregulating UCP2 through downregulation of hsa-miR-24-3p.
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Affiliation(s)
- Wenjuan Wei
- 1 Department of Cardiovascular Medicine, The First People's Hospital of Xiaoshan Hangzhou, Hangzhou, China
| | - Jun Peng
- 1 Department of Cardiovascular Medicine, The First People's Hospital of Xiaoshan Hangzhou, Hangzhou, China
| | - Ting Shen
- 2 Electrocardiogram Room of Department of Functional Examination, Zhejiang Province Tongde Hospital, Hangzhou, China
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Szemraj-Rogucka ZM, Szemraj J, Masiarek K, Majos A. Circulating microRNAs as biomarkers for myocardial fibrosis in patients with left ventricular non-compaction cardiomyopathy. Arch Med Sci 2019; 15:376-384. [PMID: 30899290 PMCID: PMC6425222 DOI: 10.5114/aoms.2019.82919] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 03/22/2017] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Despite the fact that cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a proven method for detecting myocardial fibrosis, there is a need for new and reliable serological biomarkers. Circulating miRNAs could be a practical and attractive alternative. The purpose of the study was to assess the miRNAs well established in myocardial fibrosis - miR-21, miR-29a, miR-30d and miR-133a - in the plasma of patients with left ventricular non-compaction (LVNC) that have areas of LGE assessed by CMR. MATERIAL AND METHODS We prospectively enrolled 13 adult patients (9 males and 4 females; mean age: 39 ±11.7 years) considered to meet standard CMR criteria for LVNC and 10 healthy age- and sex-matched subjects. All LVNC patients and control subjects underwent CMR examination and the measurement of peripheral plasma levels of 4 miRNAs: miR-21, miR-29a, miR-30d and miR-133a. RESULTS The LGE was present in 9 of the 13 (69.2%) LVNC patients, and most often located in the ventricular septum. Compared with LGE-negative patients, LGE-positive patients had significantly lower LVEF (28.3 ±13.3% vs. 53.5 ±14.9%, p = 0.0113) and greater LV end-diastolic diameter (67.8 ±9.5 mm vs. 57 ±2.2 mm, p = 0.01). Significant up-regulation of all 4 miRNAs was observed among LGE-positive patients vs. LGE-negative patients: miR-21 (p = 0.007), miR-29a (p = 0.0001), miR-30d (p = 0.001) and miR-133a (p = 0.0003). CONCLUSIONS The up-regulation of miR-21, miR-29a, miR-30d and miR-133a indicates the presence of LGE in LVNC patients, and therefore they may serve as potential biomarkers for myocardial fibrosis.
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Affiliation(s)
- Zofia M. Szemraj-Rogucka
- Department of Radiology and Diagnostic Imaging, Medical University of Lodz, Central Clinical Hospital, Lodz, Poland
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland
| | - Konrad Masiarek
- Department of Interventional Cardiology and Cardiac Arrhythmias, Medical University of Lodz, Medical University Teaching Hospital, Lodz, Poland
| | - Agata Majos
- Department of Radiology and Diagnostic Imaging, Medical University of Lodz, Central Clinical Hospital, Lodz, Poland
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Feng H, Wu J, Chen P, Wang J, Deng Y, Zhu G, Xian J, Huang L, Ouyang W. MicroRNA-375-3p inhibitor suppresses angiotensin II-induced cardiomyocyte hypertrophy by promoting lactate dehydrogenase B expression. J Cell Physiol 2019; 234:14198-14209. [PMID: 30618075 DOI: 10.1002/jcp.28116] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 12/21/2018] [Indexed: 01/05/2023]
Abstract
Cardiac hypertrophy is a myocardial enlargement due to overload pressure, and the primary cause of heart failure. We investigated the function of miR-375-3p in cardiac hypertrophy and its regulating mechanisms. miR-375-3p was upregulated in hearts of the transverse aortic constriction rat model and angiotensin II (Ang II)-induced primary cardiomyocyte hypertrophy model; the opposite was observed for lactate dehydrogenase B (LDHB) protein expression. miR-375-3p knockdown reduced the surface area of primary cardiomyocytes increased by Ang II treatment and decreased the B-natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) messenger RNA (mRNA) and protein levels. miR-375-3p was also observed to directly target LDHB. LDHB knockdown increased the surface area of Ang II-treated primary cardiomyocytes and increased the BNP and β-MHC mRNA and protein levels. LDHB knockdown attenuated the effects of miR-375-3p on the surface area of primary cardiomyocytes and BNP and β-MHC levels. Therefore, miR-375-3p inhibitor suppresses Ang II-induced cardiomyocyte hypertrophy by promoting LDHB expression.
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Affiliation(s)
- Huijuan Feng
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Juqing Wu
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Pan Chen
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Jing Wang
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Yuying Deng
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Guoquan Zhu
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Jialang Xian
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Liuhua Huang
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Wei Ouyang
- Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China
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What is the blood concentration of extracellular vesicles? Implications for the use of extracellular vesicles as blood-borne biomarkers of cancer. Biochim Biophys Acta Rev Cancer 2019; 1871:109-116. [DOI: 10.1016/j.bbcan.2018.11.006] [Citation(s) in RCA: 190] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 11/16/2018] [Accepted: 11/20/2018] [Indexed: 12/18/2022]
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30
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Haybar H, Shahrabi S, Shahjahani M, Rezaeeyan H. Diagnostic Value of HLA Typing in Pathogenesis of Cardiomyopathy. Cardiovasc Hematol Disord Drug Targets 2018; 19:132-138. [PMID: 30520385 DOI: 10.2174/1871529x19666181205151340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/14/2018] [Accepted: 11/07/2018] [Indexed: 11/22/2022]
Abstract
Development of cardiomyopathy (CM) is dependent upon several factors. However, the reaction of the immune response against myocardial tissue due to microbial and viral infections plays an important role in this disease. Therefore, the purpose of this study is to investigate the relationship between HLAs and their pathogenic mechanisms in the incidence of CM. Relevant literature was identified by a PubMed search (1989-2017) of English-language papers using the terms "Cardiomyopathy", "Human leukocyte antigen or HLA", "immune response", and "polymorphism". If CM patients are afflicted with viral and microbial infections, HLA class II molecules, which are not expressed on myocardial tissue in normal conditions, are mainly expressed on it. As a result, these HLAs present self- antigens and provoke autoimmune responses against myocardial tissue. On the other hand, the occurrence of polymorphism as well as disrupted expression of miRNAs can affect HLA expression, leading to hypertrophy and fibrosis of cardiac muscle. Finally, it is inferred that the expression evaluation of HLAs as well as identification of polymorphisms in their coding genes can be effective diagnostic factors in the detection of people susceptible to CM.
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Affiliation(s)
- Habib Haybar
- Atherosclerosis research center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Saeid Shahrabi
- Department of biochemistry and hematology, faculty of medicine, Semnan University of medical sciences, Semnan, Iran
| | - Mohammad Shahjahani
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hadi Rezaeeyan
- Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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31
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Onrat ST, Onrat E, Ercan Onay E, Yalım Z, Avşar A. The Genetic Determination of the Differentiation Between Ischemic Dilated Cardiomyopathy and Idiopathic Dilated Cardiomyopathy. Genet Test Mol Biomarkers 2018; 22:644-651. [DOI: 10.1089/gtmb.2018.0188] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Serap Tutgun Onrat
- Department of Medical Genetics, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | - Ersel Onrat
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | | | - Zafer Yalım
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
| | - Alaettin Avşar
- Department of Cardiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
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32
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Gupta A, Sugadev R, Sharma YK, Yahmad Y, Khurana P. Role of miRNAs in hypoxia-related disorders. J Biosci 2018; 43:739-749. [PMID: 30207319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Hypoxia is a complex pathophysiological condition. The physiological and molecular responses to this stress have been extensively studied. However, the management of its ill effects still poses a challenge to clinicians. MicroRNAs (miRNAs) are short non-coding RNA molecules that control post-transcriptional gene expression. The regulatory role of miRNAs in hypoxic environments has been studied in many hypoxia-related disorders, however a comprehensive compilation and analysis of all data and the significance of miRNAs in hypoxia adaption is still lacking. This review summarizes the miRNAs related to various hypoxia-related disorders and highlights the computational approaches to study them. This would help in designing novel strategies toward efficient management of hypoxia-related disorders.
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Affiliation(s)
- A Gupta
- Defence Institute of Physiology and Allied Sciences (DIPAS), Defence R and D Organization (DRDO), Timarpur, Delhi 110 054, India
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33
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Gupta A, Sugadev R, Sharma YK, Ahmad Y, Khurana P. Role of miRNAs in hypoxia-related disorders. J Biosci 2018. [DOI: 10.1007/s12038-018-9789-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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34
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Pakravan G, Foroughmand AM, Peymani M, Ghaedi K, Hashemi MS, Hajjari M, Nasr-Esfahani MH. Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells. Cell Death Dis 2018; 9:758. [PMID: 29988029 PMCID: PMC6037713 DOI: 10.1038/s41419-018-0797-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 06/09/2018] [Accepted: 06/14/2018] [Indexed: 12/27/2022]
Abstract
Doxorubicin (Dox) is a widely used powerful chemotherapeutic component for cancer treatment. However, its clinical application has been hampered due to doxorubicin-induced cardiomyopathy upon the cessation of chemotherapy. Previous studies revealed that PPARγ plays a crucial protective role in cardiomyocytes. Modulation of miRNA expression is an applicable approach for prohibition of toxicity induction. Therefore, the aim of present study is uprising of PPARγ transcript levels via manipulation of miRNAs to limit Dox-induced cardiotoxicity in mESCs-derived cardiac cells, as in vitro model cell to provide a simple direct approach for further clinical therapies. Based on bioinformatics data mining, eventually miR-130a was selected to target PPARγ. This miRNA is highly expressed in heart. The expression of miR-130a increases sharply upon Dox treatment while specific antagomiR-130a reverses Dox-induced reduced expression of PPARγ, cellular apoptosis, and inflammation. Our data strongly suggest that antagomiR-130a limits Dox-induced cellular toxicity via PPARγ upregulation and may have clinical relevance to limit in vivo Dox toxicity.
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Affiliation(s)
- Golnaz Pakravan
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Maryam Peymani
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.,Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Kamran Ghaedi
- Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran. .,Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
| | - Motahare-Sadat Hashemi
- Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohammadreza Hajjari
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mohammad Hossein Nasr-Esfahani
- Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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35
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Wu K, Zhao Q, Li Z, Li N, Xiao Q, Li X, Zhao Q. Bioinformatic screening for key miRNAs and genes associated with myocardial infarction. FEBS Open Bio 2018; 8:897-913. [PMID: 29928570 PMCID: PMC5985982 DOI: 10.1002/2211-5463.12423] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 03/07/2018] [Accepted: 03/23/2018] [Indexed: 12/11/2022] Open
Abstract
Despite significant advances in understanding of the causes of and treatment of myocardial infarction (MI) in recent years, morbidity and mortality is still high. The aim of this study was to identify miRNA and genes potentially associated with MI. mRNA and miRNA expression datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/). Interactions between miRNA and the expression and function of target genes were analyzed, and a protein–protein interaction network was constructed. The diagnostic value of identified miRNA and genes was assessed. Quantitative RT‐PCR was applied to validate the results of the bioinformatics analysis. MiR‐27a, miR‐31*, miR‐1291, miR‐139‐5p, miR‐204, miR‐375, and target genes including CX3CR1,HSPA6, and TPM3 had potential diagnostic value. The genes TFEB,IRS2,GRB2,FASLG,LIMS1,CX3CR1,HSPA6,TPM3,LAT2,CEBPD,AQP9, and MAPKAPK2 were associated with recovery from MI. In conclusion, the identified miRNA and genes might be associated with the pathology of MI.
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Affiliation(s)
- Ke Wu
- Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing China.,Department of Cardiology Central Hospital of Taian of Shandong Province China
| | - Qiang Zhao
- Department of Cardiology Affiliated Hospital of Taishan Medical University of Shandong Province Taian China
| | - Zhengmei Li
- Department of Radiology Taishan Medical University of Shandong Province Taian China
| | - Nannan Li
- Department of Respiration Medicine Central Hospital of Taian of Shandong Province China
| | - Qiang Xiao
- Department of Cardiology Affiliated Hospital of Taishan Medical University of Shandong Province Taian China
| | - Xiuchang Li
- Department of Cardiology Affiliated Hospital of Taishan Medical University of Shandong Province Taian China
| | - Quanming Zhao
- Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing China
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36
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Graybill RM, Cardenosa-Rubio MC, Yang H, Johnson MD, Bailey RC. Multiplexed microRNA Expression Profiling by Combined Asymmetric PCR and Label-Free Detection using Silicon Photonic Sensor Arrays. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2018; 10:1618-1623. [PMID: 30275912 PMCID: PMC6162071 DOI: 10.1039/c8ay00190a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
Analysis methods based upon the quantitative, real-time polymerase chain reaction are extremely powerful; however, they face intrinsic limitations in terms of target multiplexing. In contrast, silicon photonic microring resonators represent a modularly multiplexable sensor array technology that is well-suited to the analysis of targeted biomarker panels. In this manuscript we employ an asymmetric polymerase chain reaction approach to selectively amplify copies of cDNAs generated from targeted miRNAs before multiplexed, label-free quantitation through hybridization to microring resonator arrays pre-functionalized with capture sequences. This method, which shows applicability to low input amounts and a large dynamic range, was demonstrated for the simultaneous detection of eight microRNA targets from twenty primary brain tumor samples with expression profiles in good agreement with literature precedent.
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Affiliation(s)
- Richard M. Graybill
- Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Matthews Ave., Urbana, IL 61801, USA
| | - Maria C. Cardenosa-Rubio
- Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Matthews Ave., Urbana, IL 61801, USA
- Department of Chemistry, University of Michigan, 930 N. University Ave. Ann Arbor, MI 48104, USA
| | - Hongwei Yang
- Department of Neurological Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, USA
- Department of Neurological Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
| | - Mark D. Johnson
- Department of Neurological Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, USA
- Department of Neurological Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
| | - Ryan C. Bailey
- Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Matthews Ave., Urbana, IL 61801, USA
- Department of Chemistry, University of Michigan, 930 N. University Ave. Ann Arbor, MI 48104, USA
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Fawzy MS, Toraih EA, Hamed EO, Hussein MH, Ismail HM. Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients. Acta Cardiol 2018; 73:131-140. [PMID: 28786773 DOI: 10.1080/00015385.2017.1351243] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population. METHODS Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay. RESULTS Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile. CONCLUSIONS Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.
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Affiliation(s)
- Manal S. Fawzy
- Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
- Department of Biochemistry, Faculty of Medicine, Northern Border University, Saudi Arabia
| | - Eman A. Toraih
- Department of Histology and Cell Biology (Genetics Unit), Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Elham O. Hamed
- Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt
| | | | - Hussein M. Ismail
- Department of Cardiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
- Department of Medicine, College of Medicine, Taibah University, Almadinah Almunawwarah, Kingdom of Saudi Arabia
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Liu X, You L, Zhou R, Zhang J. Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects. Oncotarget 2018; 8:5692-5702. [PMID: 28035059 PMCID: PMC5351582 DOI: 10.18632/oncotarget.14249] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 11/30/2016] [Indexed: 01/29/2023] Open
Abstract
Molecular epidemiological studies suggest that microRNA polymorphisms may be associated with an increased risk of coronary heart disease (CHD). However, the results of these studies were inconsistent and inconclusive. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between microRNA polymorphisms and CHD risk. PubMed, Embase, CNKI and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the association between microRNA-146a rs2910164, microRNA-196a2 rs11614913, microRNA-499 rs3746444 and microRNA-149 rs71428439 polymorphisms and CHD susceptibility. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. A total of thirteen related studies involving 8,120 patients and 8,364 controls were analyzed. Significant associations between microRNA-146a rs2910164 polymorphism and CHD risk were observed in the total population, as well as in subgroup analysis. For microRNA-196a2 rs11614913 and microRNA-499 rs3746444, similarly increased risks were also found. In addition, no significant association was detected between microRNA-149 rs71428439 polymorphism and CHD risk. In conclusion, our meta-analyses suggest that microRNA polymorphisms may be associated with increased risk of CHD development.
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Affiliation(s)
- Xu Liu
- Department of Neurology, First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, China
| | - Lianghao You
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
| | - Ruizhi Zhou
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
| | - Jian Zhang
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
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Bian JT, Piano MR, Kotlo KU, Mahmoud AM, Phillips SA. MicroRNA-21 Contributes to Reduced Microvascular Function in Binge Drinking Young Adults. Alcohol Clin Exp Res 2018; 42:278-285. [PMID: 29178290 PMCID: PMC7286284 DOI: 10.1111/acer.13565] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Accepted: 11/20/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Binge drinking is associated with increased risk for cardiovascular (CV) disease. MicroRNA-21 (miR21) is up-regulated in the setting of excessive alcohol consumption and CV disease. Therefore, the goal of this study was to examine the vasodilatory responses to flow and acetylcholine (ACh) in the absence and presence of an anti-miR21 inhibitor in the microcirculation of young adult repeated binge drinkers (BDs). METHODS Gluteal subcutaneous adipose tissue biopsies were obtained from young adults (18 to 30 years, n = 35 vessels from BDs and n = 28 vessels from abstainers). Resistance arteries (RAs) were isolated, incubated with anti-miR21 or a negative control (NC) to miR21 (12 hours; 50 nM), and lumen diameters measured with video microscopy. miR21 of adipose tissues was determined by quantitative polymerase chain reaction. RESULTS Flow-induced dilation and ACh-induced dilation (AChID) were reduced in BDs as compared to abstainers. The miR21 inhibitor but not the NC abrogated these effects in BDs, but did not affect vasodilation in abstainers. Nitric oxide synthase inhibition with L-NAME reduced vasodilation in abstainers but not in BDs. In BDs, vasodilation was reduced by L-NAME in the presence of anti-miR21 but not the NC. Scavenging the reactive oxygen species, hydrogen peroxide with polyethylene glycol catalase reduced dilation in BDs but did not affect the restored dilation by the miR21 inhibitor. Maximum dilation to papaverine (endothelium independent) was similar between groups and unaffected by pharmacological inhibition. Finally, vascular endogenous miR21 was increased in BDs compared to abstainers. CONCLUSIONS Endogenous miR21 is increased in RAs of young BDs, leading to reduced flow and AChID in the microcirculation.
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Affiliation(s)
- Jing-Tan Bian
- Department of Biobehavioral Health Science, University of
Illinois at Chicago, Chicago, Illinois
| | - Mariann R. Piano
- Department of Biobehavioral Health Science, University of
Illinois at Chicago, Chicago, Illinois
- School of Nursing, Vanderbilt University, Nashville,
TN
| | - Kumar U. Kotlo
- Division of Cardiology, Department of Medicine, University
of Illinois at Chicago, Chicago, IL
| | - Abeer M. Mahmoud
- Department of Physical Therapy, University of Illinois at
Chicago, Chicago, IL
- Department of Kinesiology and Nutrition, University of
Illinois at Chicago, Chicago, IL
| | - Shane A. Phillips
- Department of Physical Therapy, University of Illinois at
Chicago, Chicago, IL
- Integrative Physiology Laboratory, University of Illinois
at Chicago, Chicago, IL
- Division of Endocrinology, Diabetes, and Metabolism,
Department of Medicine, University of Illinois at Chicago, Chicago, IL
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40
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Nanoudis S, Pikilidou M, Yavropoulou M, Zebekakis P. The Role of MicroRNAs in Arterial Stiffness and Arterial Calcification. An Update and Review of the Literature. Front Genet 2017; 8:209. [PMID: 29312437 PMCID: PMC5733083 DOI: 10.3389/fgene.2017.00209] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 11/28/2017] [Indexed: 12/20/2022] Open
Abstract
Arterial stiffness is an independent risk factor for fatal and non-fatal cardiovascular events, such as systolic hypertension, coronary artery disease, stroke, and heart failure. Moreover it reflects arterial aging which in many cases does not coincide with chronological aging, a fact that is in large attributed to genetic factors. In addition to genetic factors, microRNAs (miRNAs) seem to largely affect arterial aging either by advancing or by regressing arterial stiffness. MiRNAs are small RNA molecules, ~22 nucleotides long that can negatively control their target gene expression posttranscriptionally. Pathways that affect main components of stiffness such as fibrosis and calcification seem to be influenced by up or downregulation of specific miRNAs. Identification of this aberrant production of miRNAs can help identify epigenetic changes that can be therapeutic targets for prevention and treatment of vascular diseases. The present review summarizes the specific role of the so far discovered miRNAs that are involved in pathways of arterial stiffness.
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Affiliation(s)
- Sideris Nanoudis
- Hypertension Excellence Center, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
| | - Maria Pikilidou
- Hypertension Excellence Center, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
| | - Maria Yavropoulou
- Division of Endocrinology and Metabolism, AHEPA University Hospital, Thessaloniki, Greece
| | - Pantelis Zebekakis
- Hypertension Excellence Center, 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
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Jiang J, Mo H, Liu C, Wu B, Wu Z, Li X, Li T, He S, Li S, You Q, Wu K, Guo R. Inhibition of miR-186-5p contributes to high glucose-induced injury in AC16 cardiomyocytes. Exp Ther Med 2017; 15:627-632. [PMID: 29399065 PMCID: PMC5772612 DOI: 10.3892/etm.2017.5445] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 01/04/2017] [Indexed: 01/12/2023] Open
Abstract
A growing body of evidence has demonstrated that microRNAs (miRs) have pivotal roles in the pathophysiological development mechanisms of diabetic cardiomyopathy (DCM). Previous studies have demonstrated that miR-186-5p was significantly decreased in DCM. In addition, it has recently been reported that an imbalance of miR-186 is associated with a variety of physiological and pathological processes. Therefore, the present study was designed to investigate the role of miR-186-5p in high glucose (HG)-induced cytotoxicity and apoptosis in AC16 cardiomyocytes. Reverse transcription-polymerase chain reaction was used to demonstrate the significant decrease in the level of miR-186-5p in HG-treated AC16 cells (P<0.05). Subsequently, it was clarified that pre-transfection with miR-186-5p mimic significantly ameliorated the effects of high glucose, which induced a significant decrease in the viability of AC16 cells (P<0.05) and increases in apoptosis, as evidenced by the appearance of apoptotic nucleus and the significant upregulation of apoptosis rate in AC16 cells (P<0.05). In addition, the significantly increased expression of caspase-3 induced by HG (P<0.01) was also reversed by miR-186-5p mimic (P<0.01). Conversely, transfection with miR-186-5p inhibitor significantly reduced the viability of AC16 cells (P<0.05) and promoted apoptosis (P<0.05) as well as the expression of caspase-3 in AC16 cells (P<0.01), indicating the beneficial role of miR-186-5p in the physiological process of HG-induced damage. In conclusion, these results suggest that the distribution of miR-186-5p contributes to HG-induced cytotoxicity and apoptosis in AC16 cardiomyocytes.
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Affiliation(s)
- Jiamei Jiang
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Hailiang Mo
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Chang Liu
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Bin Wu
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Zijun Wu
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Xingyue Li
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Teng Li
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Songjian He
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Shanghai Li
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Qiong You
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Keng Wu
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Runmin Guo
- Department of Cardiology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
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miR-21-5p is associated with the regulation of estradiol benzoate and oxytocin induced primary dysmenorrhea in rat uterus: a bioinformatic study. Genes Genomics 2017. [DOI: 10.1007/s13258-017-0591-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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43
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Ruan L, Yang Y, Huang Y, Ding L, Zhang C, Wu X. Functional prediction of miR-3144-5p in human cardiac myocytes based on transcriptome sequencing and bioinformatics. Medicine (Baltimore) 2017; 96:e7539. [PMID: 28796037 PMCID: PMC5556203 DOI: 10.1097/md.0000000000007539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics. Transcriptome sequencing was then performed in HCMs with or without transfection. The sequencing results were subjected to bioinformatic analyses, including differentially expressed gene (DEG) analysis, functional enrichment analysis, protein-protein interaction (PPI) network analysis, miRNA-target gene analysis, and miRNA-transcription factor (TF)-target gene coregulatory network analysis. RESULTS There really existed a regulatory relation between miR-3144-5p and RANGRF. The expression level of miR-3144-5p was low in HCMs. After cell transfection, miR-3144-5p expression level significantly increased in HCMs. Bioinformatic analyses of the transcriptome sequencing results identified 300 upregulated and 271 downregulated DEGs between miR-3144-5p mimic and control group. The upregulated genes ISL1 and neuregulin 1 (NRG1) were significantly enriched in cardiac muscle cell myoblast differentiation (GO:0060379). CCL21 was one of the hub genes in the PPI network and also a target gene of miR-3144-5p. Moreover, the TF of v-Myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN) was involved in the miR-3144-5p-TF-target gene coregulatory network and interacted with the target genes of miR-3144-5p. CONCLUSION ISL1, NRG1, CCL21, and MYCN were differentially expressed in the miR-3144-5p mimic group, suggesting that miR-3144-5p overexpression plays a role in HCMs by regulating these genes and TF. This study may provide new insight into the mechanisms behind the progression of cardiac arrhythmia.
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44
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Wilson RA, Deasy W, Hayes A, Cooke MB. High fat diet and associated changes in the expression of micro-RNAs in tissue: Lessons learned from animal studies. Mol Nutr Food Res 2017; 61. [PMID: 28233461 DOI: 10.1002/mnfr.201600943] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 01/15/2017] [Accepted: 02/13/2017] [Indexed: 12/13/2022]
Abstract
Environment and genetic factors play an important role in the development of obesity, and diet is one of the main contributing factors to this disease. High fat intake is associated with body weight gain, leading to obesity and other metabolic diseases. MicroRNAs (miRNAs) are a group of small, noncoding RNAs that are important regulators of gene expression at posttranscriptional level. Studies have shown that high fat intake, independent of body weight status, can significantly impact both negatively and positively the expression of miRNAs and thus the biological function of tissues such as adipose, skeletal, and cardiac muscle, liver, neuronal, and endothelial. This review will summarize the effects of high calorie diet in the form of high fat intake on miRNA expression in various tissues of animal models and of high fat fed offspring. We will also briefly review the impact of different dietary lipids on miRNA expression. Given changes in miRNA expression have been associated with the development of many diseases including obesity, understanding their biological role could have important clinical implications and offer tangible therapeutic targets for the prevention, management, and/or treatment of obesity and other lifestyle-related disorders.
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Affiliation(s)
- Robin A Wilson
- College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), Western Health, Melbourne, VIC, Australia
| | - William Deasy
- College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), Western Health, Melbourne, VIC, Australia
| | - Alan Hayes
- College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), Western Health, Melbourne, VIC, Australia
| | - Matthew B Cooke
- College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), Western Health, Melbourne, VIC, Australia
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45
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Parthenakis F, Marketou M, Kontaraki J, Patrianakos A, Nakou H, Touloupaki M, Vernardos M, Kochiadakis G, Chlouverakis G, Vardas P. Low Levels of MicroRNA-21 Are a Marker of Reduced Arterial Stiffness in Well-Controlled Hypertension. J Clin Hypertens (Greenwich) 2017; 19:235-240. [PMID: 27550546 PMCID: PMC8031006 DOI: 10.1111/jch.12900] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/13/2016] [Accepted: 07/23/2016] [Indexed: 11/28/2022]
Abstract
MicroRNAs (miRNAs) play a crucial role in myocardial and vascular remodeling and have emerged as potential diagnostic and prognostic biomarkers or as therapeutic targets. The authors aimed to investigate the expression profile of selected miRNAs in the peripheral blood of patients with well-controlled essential hypertension in relation to arterial stiffness. Expression levels of miRNAs miRNA-1, miRNA-133a, miRNA-26b, miRNA-208b, miRNA-499, and miRNA-21 in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Carotid-femoral pulse wave velocity (cfPWV) and carotid radial pulse wave velocity (crPWV) were evaluated at baseline and after 1 year of effective antihypertensive therapy. A total of 95 patients (50 men, mean age 62±9 years) with well-controlled essential hypertension were included in the analysis. Only miRNA-21 was independently correlated with changes in both cfPWV and crPWV, independently of blood pressure levels (r=-0.56 and r=-0.46, respectively; P<.001 for both). Low levels of miRNA-21 are strongly associated with an improvement in arterial stiffness in patients with well-controlled essential hypertension, independently of their blood pressure levels. These data highlight the significance of miRNA-21 in vascular remodeling and its role as a potential prognostic marker and future therapeutic target.
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Affiliation(s)
| | - Maria Marketou
- Cardiology DepartmentHeraklion University HospitalCreteGreece
| | - Joanna Kontaraki
- Molecular Cardiology LaboratorySchool of MedicineUniversity of CreteHeraklionGreece
| | | | - Helen Nakou
- Cardiology DepartmentHeraklion University HospitalCreteGreece
| | | | | | | | | | - Panos Vardas
- Cardiology DepartmentHeraklion University HospitalCreteGreece
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Parra V, Rothermel BA. Calcineurin signaling in the heart: The importance of time and place. J Mol Cell Cardiol 2017; 103:121-136. [PMID: 28007541 PMCID: PMC5778886 DOI: 10.1016/j.yjmcc.2016.12.006] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 12/12/2016] [Accepted: 12/16/2016] [Indexed: 12/20/2022]
Abstract
The calcium-activated protein phosphatase, calcineurin, lies at the intersection of protein phosphorylation and calcium signaling cascades, where it provides an essential nodal point for coordination between these two fundamental modes of intracellular communication. In excitatory cells, such as neurons and cardiomyocytes, that experience rapid and frequent changes in cytoplasmic calcium, calcineurin protein levels are exceptionally high, suggesting that these cells require high levels of calcineurin activity. Yet, it is widely recognized that excessive activation of calcineurin in the heart contributes to pathological hypertrophic remodeling and the progression to failure. How does a calcium activated enzyme function in the calcium-rich environment of the continuously contracting heart without pathological consequences? This review will discuss the wide range of calcineurin substrates relevant to cardiovascular health and the mechanisms calcineurin uses to find and act on appropriate substrates in the appropriate location while potentially avoiding others. Fundamental differences in calcineurin signaling in neonatal verses adult cardiomyocytes will be addressed as well as the importance of maintaining heterogeneity in calcineurin activity across the myocardium. Finally, we will discuss how circadian oscillations in calcineurin activity may facilitate integration with other essential but conflicting processes, allowing a healthy heart to reap the benefits of calcineurin signaling while avoiding the detrimental consequences of sustained calcineurin activity that can culminate in heart failure.
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Affiliation(s)
- Valentina Parra
- Advanced Centre for Chronic Disease (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago,Chile; Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chie, Santiago, Chile
| | - Beverly A Rothermel
- Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Centre, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Centre, Dallas, TX, USA.
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47
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Dioni L, Sucato S, Motta V, Iodice S, Angelici L, Favero C, Cavalleri T, Vigna L, Albetti B, Fustinoni S, Bertazzi P, Pesatori A, Bollati V. Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects. Eur J Clin Nutr 2017; 71:142-148. [PMID: 27731332 PMCID: PMC5222989 DOI: 10.1038/ejcn.2016.197] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 08/09/2016] [Accepted: 08/20/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND/OBJECTIVES Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. SUBJECTS/METHODS We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. RESULTS Urinary Cr levels (mean: 0.35 μg/l; s.d.=0.24) ranged from 0.05 to 1.27 μg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (β=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (β=2.1; P=0.004) and systolic BP (β=3.3; P=0.003). CONCLUSIONS These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs.
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Affiliation(s)
- L Dioni
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - S Sucato
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - V Motta
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - S Iodice
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - L Angelici
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - C Favero
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - T Cavalleri
- Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - L Vigna
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Preventive Medicine, Milan, Italy
| | - B Albetti
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - S Fustinoni
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Preventive Medicine, Milan, Italy
| | - P Bertazzi
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Preventive Medicine, Milan, Italy
| | - A Pesatori
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Preventive Medicine, Milan, Italy
| | - V Bollati
- EPIGET—Epidemiology, Epigenetics and Toxicology Lab—Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Preventive Medicine, Milan, Italy
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Lai CQ, Wojczynski MK, Parnell LD, Hidalgo BA, Irvin MR, Aslibekyan S, Province MA, Absher DM, Arnett DK, Ordovás JM. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge. J Lipid Res 2016; 57:2200-2207. [PMID: 27777315 PMCID: PMC5321216 DOI: 10.1194/jlr.m069948] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 10/16/2016] [Indexed: 12/18/2022] Open
Abstract
Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10−7), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD.
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Affiliation(s)
- Chao-Qiang Lai
- USDA Agricultural Research Service, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
| | - Mary K Wojczynski
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
| | - Laurence D Parnell
- USDA Agricultural Research Service, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
| | - Bertha A Hidalgo
- Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL
| | - Marguerite Ryan Irvin
- Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL
| | - Stella Aslibekyan
- Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL
| | - Michael A Province
- Department of Genetics, Washington University School of Medicine, St. Louis, MO
| | - Devin M Absher
- Hudson Alpha Institute for Biotechnology, Huntsville, AL
| | - Donna K Arnett
- College of Public Health, University of Kentucky, Lexington, KY
| | - José M Ordovás
- Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
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49
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Zhu YP, Thomas GD, Hedrick CC. 2014 Jeffrey M. Hoeg Award Lecture: Transcriptional Control of Monocyte Development. Arterioscler Thromb Vasc Biol 2016; 36:1722-33. [PMID: 27386937 PMCID: PMC5828163 DOI: 10.1161/atvbaha.116.304054] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 06/24/2016] [Indexed: 01/01/2023]
Abstract
Monocytes and macrophages are key immune cells involved in the early progression of atherosclerosis. Transcription factors that control their development in the bone marrow are important therapeutic targets to control the numbers and functions of these cells in disease. This review highlights what is currently known about the transcription factors that are critical for monocyte development.
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Affiliation(s)
- Yanfang Peipei Zhu
- From the Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, CA
| | - Graham D Thomas
- From the Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, CA
| | - Catherine C Hedrick
- From the Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, CA.
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50
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Ruddy JM, Ikonomidis JS, Jones JA. Multidimensional Contribution of Matrix Metalloproteinases to Atherosclerotic Plaque Vulnerability: Multiple Mechanisms of Inhibition to Promote Stability. J Vasc Res 2016; 53:1-16. [PMID: 27327039 PMCID: PMC7196926 DOI: 10.1159/000446703] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 05/07/2016] [Indexed: 12/17/2022] Open
Abstract
The prevalence of atherosclerotic disease continues to increase, and despite significant reductions in major cardiovascular events with current medical interventions, an additional therapeutic window exists. Atherosclerotic plaque growth is a complex integration of cholesterol penetration, inflammatory cell infiltration, vascular smooth muscle cell (VSMC) migration, and neovascular invasion. A family of matrix-degrading proteases, the matrix metalloproteinases (MMPs), contributes to all phases of vascular remodeling. The contribution of specific MMPs to endothelial cell integrity and VSMC migration in atherosclerotic lesion initiation and progression has been confirmed by the increased expression of these proteases in plasma and plaque specimens. Endogenous blockade of MMPs by the tissue inhibitors of metalloproteinases (TIMPs) may attenuate proteolysis in some regions, but the progression of matrix degeneration suggests that MMPs predominate in atherosclerotic plaque, precipitating vulnerability. Plaque neovascularization also contributes to instability and, coupling the known role of MMPs in angiogenesis to that of atherosclerotic plaque growth, interest in targeting MMPs to facilitate plaque stabilization continues to accumulate. This article aims to review the contributions of MMPs and TIMPs to atherosclerotic plaque expansion, neovascularization, and rupture vulnerability with an interest in promoting targeted therapies to improve plaque stabilization and decrease the risk of major cardiovascular events.
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Affiliation(s)
- Jean Marie Ruddy
- Division of Vascular Surgery, Department of Surgery, Medical University of South Carolina, Charleston, S.C., USA
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