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Dornas W, Silva M. Modulation of the antioxidant enzyme paraoxonase-1 for protection against cardiovascular diseases. Nutr Metab Cardiovasc Dis 2024; 34:2611-2622. [PMID: 39277536 DOI: 10.1016/j.numecd.2024.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/12/2024] [Accepted: 04/04/2024] [Indexed: 09/17/2024]
Abstract
AIM The enzyme paraoxonase 1 (PON1) bound to high-density lipoprotein has received special attention for its protective role against stress-mediated damage and use as a potential regulatory target in atherosclerosis and related vascular diseases. DATA SYNTHESIS We present an overview of the literature on PON1 activity and mRNA levels by investigating its modulation for clinical translations. Specifically, the expression of PON1 and its regulated activity can be modified in different ways with natural substances, drugs, and lifestyle factors thar affect the development of atherosclerosis. CONCLUSIONS The endothelial contribution of PON1 to overcome differences considering an individual's disease development risk is supported by polymorphism interaction data and the susceptibility to modify PON1 responses in chronic events composed by biological and environmental factors.
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Affiliation(s)
- Waleska Dornas
- Course Superior of Technology in Radiology, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
| | - Maisa Silva
- Department of Basic Life Sciences, Universidade Federal de Juiz de Fora, Governador Valadares, MG, Brazil
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2
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Afzal M, Greco F, Quinzi F, Scionti F, Maurotti S, Montalcini T, Mancini A, Buono P, Emerenziani GP. The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases-A Systematic Review. Int J Mol Sci 2024; 25:6813. [PMID: 38999923 PMCID: PMC11240922 DOI: 10.3390/ijms25136813] [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: 04/16/2024] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 07/14/2024] Open
Abstract
Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways' regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in the prognosis and treatment of NCDs and important epigenetic factors, miRNAs, play a crucial role in cellular pathways. This systematic review aims to underline the potential link between changes in miRNA expression after different types of physical activity/exercise in some populations affected by NCDs. In June 2023, we systematically investigated the following databases: PubMed, MEDLINE, Scopus, and Web of Science, on the basis of our previously established research questions and following the PRISMA guidelines. The risk of bias and quality assessment were, respectively, covered by ROB2 and the Newcastle Ottawa scale. Of the 1047 records extracted from the initial search, only 29 studies were found to be eligible. In these studies, the authors discuss the association between exercise-modulated miRNAs and NCDs. The NCDs included in the review are cancer, cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus (T2DM). We evidenced that miR-146, miR-181, miR-133, miR-21, and miRNA-1 are the most reported miRNAs that are modulated by exercise. Their expression is associated with an improvement in health markers and they may be a potential target in terms of the development of future therapeutic tools.
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Affiliation(s)
- Moomna Afzal
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
| | - Francesca Greco
- Department of Movement, Human and Health Sciences, Foro Italico University of Rome, 00135 Rome, Italy
| | - Federico Quinzi
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
| | - Francesca Scionti
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
| | - Samantha Maurotti
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
- Research Center for the Prevention and Treatment of Metabolic Diseases, University Magna Grecia, 88100 Catanzaro, Italy
| | - Annamaria Mancini
- Department of Medicine, Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy
- CEINGE-Biotecnologie Avanzate Franco Salvatore s.r.l, 80131 Naples, Italy
| | - Pasqualina Buono
- Department of Medicine, Movement Sciences and Wellbeing, University Parthenope, 80133 Naples, Italy
- CEINGE-Biotecnologie Avanzate Franco Salvatore s.r.l, 80131 Naples, Italy
| | - Gian Pietro Emerenziani
- Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy
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Biernat K, Kuciel N, Mazurek J, Hap K. Is It Possible to Train the Endothelium?-A Narrative Literature Review. Life (Basel) 2024; 14:616. [PMID: 38792637 PMCID: PMC11121998 DOI: 10.3390/life14050616] [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: 03/22/2024] [Revised: 05/03/2024] [Accepted: 05/04/2024] [Indexed: 05/26/2024] Open
Abstract
This review provides an overview of current knowledge regarding the adaptive effects of physical training on the endothelium. The endothelium plays a crucial role in maintaining the health of vessel walls and regulating vascular tone, structure, and homeostasis. Regular exercise, known for its promotion of cardiovascular health, can enhance endothelial function through various mechanisms. The specific health benefits derived from exercise are contingent upon the type and intensity of physical training. The review examines current clinical evidence supporting exercise's protective effects on the vascular endothelium and identifies potential therapeutic targets for endothelial dysfunction. There is an urgent need to develop preventive strategies and gain a deeper understanding of the distinct impacts of exercise on the endothelium.
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Affiliation(s)
| | - Natalia Kuciel
- University Rehabilitation Centre, Wroclaw Medical University, 50-367 Wroclaw, Poland; (K.B.); (J.M.); (K.H.)
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Shrivastav D, Singh DD. Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus. World J Clin Cases 2024; 12:525-537. [PMID: 38322458 PMCID: PMC10841963 DOI: 10.12998/wjcc.v12.i3.525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/18/2023] [Accepted: 01/03/2024] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Uncontrolled high sugar levels lead to advanced glycation end products (AGEs), which affects several metabolic pathways by its receptor of advanced glycation end products (RAGE) and causes diabetic complication. MiRNAs are small RNA molecules which regulate genes linked to diabetes and affect AGEs pathogenesis, and target tissues, influencing health and disease processes. AIM To explore miRNA roles in T2DM's metabolic pathways for potential therapeutic and diagnostic advancements in diabetes complications. METHODS We systematically searched the electronic database PubMed using keywords. We included free, full-length research articles that evaluate the role of miRNAs in T2DM and its complications, focusing on genetic and molecular disease mechanisms. After assessing the full-length papers of the shortlisted articles, we included 12 research articles. RESULTS Several types of miRNAs are linked in metabolic pathways which are affected by AGE/RAGE axis in T2DM and its complications. miR-96-5p, miR-7-5p, miR-132, has_circ_0071106, miR-143, miR-21, miR-145-5p, and more are associated with various aspects of T2DM, including disease risk, diagnostic markers, complications, and gene regulation. CONCLUSION Targeting the AGE/RAGE axis, with a focus on miRNA regulation, holds promise for managing T2DM and its complications. MiRNAs have therapeutic potential as they can influence the metabolic pathways affected by AGEs and RAGE, potentially reducing inflammation, oxidative stress, and vascular complications. Additionally, miRNAs may serve as early diagnostic biomarkers for T2DM. Further research in this area may lead to innovative therapeutic strategies for diabetes and its associated complications.
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Affiliation(s)
| | - Desh Deepak Singh
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India
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Bacchetti T, Morresi C, Ferretti G, Larsson A, Åkerfeldt T, Svensson M. Effects of Seven Weeks of Combined Physical Training on High-Density Lipoprotein Functionality in Overweight/Obese Subjects. Metabolites 2023; 13:1068. [PMID: 37887393 PMCID: PMC10609075 DOI: 10.3390/metabo13101068] [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: 09/02/2023] [Revised: 09/28/2023] [Accepted: 10/06/2023] [Indexed: 10/28/2023] Open
Abstract
Our study aimed to investigate the effects of exercise on HDL composition and functional properties in overweight/obese subjects. Eighteen overweight/obese subjects (nine F and nine M, BMI = 30.3 ± 3 kg/m2) attended supervised training for 7 weeks. The protocol included combined resistance and conditioning training four to five times each week. The activity of the antioxidant enzyme paraoxonase-1 (PON1) associated with HDL was evaluated in all subjects before and after the training intervention. Moreover, myeloperoxidase (MPO) levels and oxidative stress markers (ox-LDLs and total antioxidant capacity) were studied in the serums of the subjects. At the end of the intervention, the activity of PON1 was increased (p < 0.0001), and MPO levels and the MPO/PON1 ratio were decreased (p < 0.0001). In addition, a significant improvement in muscle strength and maximal oxygen uptake (VO2max) (p < 0.0001) and a significant reduction in total and visceral adipose tissue mass (p < 0.001) and waist circumference (p < 0.008), without any significant decrease in body weight, were observed. A significant correlation was established between serum MPO/PON ratios, HDL redox activity and ox-LDLs. In conclusion, our results demonstrate that exercise training, without modifications of dietary habits, improved HDL functionality in overweight/obese adults, without any significant reduction in BMI or modifications of glucose and lipid biochemical parameters.
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Affiliation(s)
- Tiziana Bacchetti
- Department of Life and Environmental Sciences, Marche Polytechnic University, Via Brecce Bianche, 60131 Ancona, Italy;
| | - Camilla Morresi
- Department of Life and Environmental Sciences, Marche Polytechnic University, Via Brecce Bianche, 60131 Ancona, Italy;
| | - Gianna Ferretti
- Department of Clinical Science and Odontostomatology, Marche Polytechnic University, Via Brecce Bianche, 60131 Ancona, Italy;
- Center for Health Promotion, Marche Polytechnic University, Via Brecce Bianche, 60131 Ancona, Italy
| | - Anders Larsson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden; (A.L.); (T.Å.)
| | - Torbjörn Åkerfeldt
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden; (A.L.); (T.Å.)
| | - Michael Svensson
- Section of Sports Medicine, Department of Community Medicine and Rehabilitation, Umeå University, 90 187 Umeå, Sweden;
- Umeå School of Sport Sciences, Umeå University, 90 187 Umeå, Sweden
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Gao J, Pan X, Li G, Chatterjee E, Xiao J. Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases. J Cardiovasc Transl Res 2021; 15:604-620. [PMID: 34533746 PMCID: PMC8447895 DOI: 10.1007/s12265-021-10171-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/02/2021] [Indexed: 12/16/2022]
Abstract
Increasing evidence shows that endothelial cells play critical roles in maintaining vascular homeostasis, regulating vascular tone, inhibiting inflammatory response, suppressing lipid leakage, and preventing thrombosis. The damage or injury of endothelial cells induced by physical, chemical, and biological risk factors is a leading contributor to the development of mortal cardiovascular and cerebrovascular diseases. However, the underlying mechanism of endothelial injury remains to be elucidated. Notably, no drugs effectively targeting and mending injured vascular endothelial cells have been approved for clinical practice. There is an urgent need to understand pathways important for repairing injured vasculature that can be targeted with novel therapies. Exercise training-induced protection to endothelial injury has been well documented in clinical trials, and the underlying mechanism has been explored in animal models. This review mainly summarizes the protective effects of exercise on vascular endothelium and the recently identified potential therapeutic targets for endothelial dysfunction.
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Affiliation(s)
- Juan Gao
- Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China
| | - Xue Pan
- Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China
| | - Guoping Li
- Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Emeli Chatterjee
- Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Junjie Xiao
- Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China. .,Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai, 200444, China.
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Wróblewski A, Strycharz J, Świderska E, Balcerczyk A, Szemraj J, Drzewoski J, Śliwińska A. Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes. Int J Mol Sci 2021; 22:ijms22136964. [PMID: 34203452 PMCID: PMC8268546 DOI: 10.3390/ijms22136964] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/12/2022] Open
Abstract
Adipokines secreted by hypertrophic visceral adipose tissue (VAT) instigate low-grade inflammation, followed by hyperglycemia (HG)-related metabolic disorders. The latter may develop with the participation of epigenetic modifications. Our aim was to assess how HG influences selected epigenetic modifications and the expression of interleukin 6 (IL-6) and adiponectin (APN; gene symbol ADIPOQ) during the adipogenesis of human visceral preadipocytes (HPA-v). Adipocytes (Ads) were chronically or transiently HG-treated during three stages of adipogenesis (proliferation, differentiation, maturation). We measured adipokine mRNA, protein, proven or predicted microRNA expression (RT-qPCR and ELISA), and enrichment of H3K9/14ac, H3K4me3, and H3K9me3 at gene promoter regions (chromatin immunoprecipitation). In chronic HG, we detected different expression patterns of the studied adipokines at the mRNA and protein levels. Chronic and transient HG-induced changes in miRNA (miR-26a-5p, miR-26b-5p, let-7d-5p, let-7e-5p, miR-365a-3p, miR-146a-5p) were mostly convergent to altered IL-6 transcription. Alterations in histone marks at the IL6 promoter were also in agreement with IL-6 mRNA. The open chromatin marks at the ADIPOQ promoter mostly reflected the APN transcription during NG adipogenesis, while, in the differentiation stage, HG-induced changes in all studied marks were in line with APN mRNA levels. In summary, HG dysregulated adipokine expression, promoting inflammation. Epigenetic changes coexisted with altered expression of adipokines, especially for IL-6; therefore, epigenetic marks induced by transient HG may act as epi-memory in Ads. Such changes in the epigenome and expression of adipokines could be instrumental in the development of inflammation and metabolic deregulation of VAT.
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Affiliation(s)
- Adam Wróblewski
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland; (J.S.); (E.Ś.); (J.S.)
- Correspondence: (A.W.); (A.Ś.)
| | - Justyna Strycharz
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland; (J.S.); (E.Ś.); (J.S.)
| | - Ewa Świderska
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland; (J.S.); (E.Ś.); (J.S.)
| | - Aneta Balcerczyk
- Department of Molecular Biophysics, University of Lodz, 90-236 Lodz, Poland;
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland; (J.S.); (E.Ś.); (J.S.)
| | - Józef Drzewoski
- Central Teaching Hospital of the Medical University of Lodz, 92-213 Lodz, Poland;
| | - Agnieszka Śliwińska
- Department of Nucleic Acids Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
- Correspondence: (A.W.); (A.Ś.)
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Evans WS, Sapp RM, Kim KI, Heilman JM, Hagberg J, Prior SJ. Effects of Exercise Training on the Paracrine Function of Circulating Angiogenic Cells. Int J Sports Med 2020; 42:1047-1057. [PMID: 33124014 DOI: 10.1055/a-1273-8390] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Exercise training has various benefits on cardiovascular health, and circulating angiogenic cells have been proposed as executing these changes. Work from the late 1990s supported an important role of these circulating post-natal cells in contributing to the maintenance and repair of the endothelium and vasculature. It was later found that circulating angiogenic cells were a heterogenous population of cells and primarily functioned in a paracrine manner by adhering to damaged endothelium and releasing growth factors. Many studies have discovered novel circulating angiogenic cell secreted proteins, microRNA and extracellular vesicles that mediate their angiogenic potential, and some studies have shown that both acute and chronic aerobic exercise training have distinct benefits. This review highlights work establishing an essential role of secreted factors from circulating angiogenic cells and summarizes studies regarding the effects of exercise training on these factors. Finally, we highlight the various gaps in the literature in hopes of guiding future work.
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Affiliation(s)
- William S Evans
- Department of Kinesiology, University of Maryland School of Public Health, College Park
| | - Ryan M Sapp
- Department of Kinesiology, University of Maryland School of Public Health, College Park
| | - Katherine I Kim
- Department of Kinesiology, University of Maryland School of Public Health, College Park
| | - James M Heilman
- Department of Kinesiology, University of Maryland School of Public Health, College Park
| | - James Hagberg
- Department of Kinesiology, University of Maryland School of Public Health, College Park
| | - Steven J Prior
- Department of Kinesiology, University of Maryland School of Public Health, College Park.,Baltimore Veterans Affairs Geriatric Research, Education and Clinical Center, Department of Veterans Affairs, Baltimore
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9
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Affiliation(s)
- Jin Hwa Kim
- Department of Endocrinology and Metabolism, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea.
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