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Coperchini F, Greco A, Teliti M, Croce L, Chytiris S, Magri F, Gaetano C, Rotondi M. Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing. Cytokine Growth Factor Rev 2025; 82:31-42. [PMID: 39237438 DOI: 10.1016/j.cytogfr.2024.08.004] [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: 07/29/2024] [Accepted: 08/20/2024] [Indexed: 09/07/2024]
Abstract
Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the "Hallmarks of ageing". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.
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Affiliation(s)
- Francesca Coperchini
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy
| | - Alessia Greco
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy
| | - Marsida Teliti
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia 27100, Italy
| | - Laura Croce
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia 27100, Italy
| | - Spyridon Chytiris
- Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia 27100, Italy
| | - Flavia Magri
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia 27100, Italy
| | - Carlo Gaetano
- Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Mario Rotondi
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Italy; Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia 27100, Italy.
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Rafaqat S, Azam A, Hafeez R, Faseeh H, Tariq M, Asif M, Arshad A, Noshair I. Role of interleukins in the pathogenesis of coronary heart disease: A literature review. World J Cardiol 2025; 17:103947. [DOI: 10.4330/wjc.v17.i3.103947] [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: 12/04/2024] [Revised: 01/22/2025] [Accepted: 02/10/2025] [Indexed: 03/21/2025] Open
Abstract
Interleukins (ILs), a subset of cytokines, play a critical role in the pathogenesis of coronary heart disease (CHD) by mediating inflammation. This review article summarizes the role of ILs such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in the pathogenesis of CHD. Individuals with mild coronary artery disease (CAD) and angina who have ischemic heart disease have higher serum concentrations of IL-1b. Larger studies are needed to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment. IL-3 is found more often in patients receiving coronary angioplasty compared to patients with asymptomatic CAD or without CAD. Serum levels of IL-4 are reliable indicators of CAD. An independent correlation between IL-5 and the incidence of CAD was demonstrated. IL-6 helps serve as a reliable biomarker for the degree of CAD, as determined by the Gensini score, and is a key factor in the development of atherosclerosis. Also, variants of IL-7/7R have been linked to the Han Chinese population's genetic susceptibility to CHD. IL-8 plays a role in the progression of CAD occurrences. By interacting with conventional risk factors for CAD, IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management. There was a 34% increased risk of a CHD incident for every standard deviation rise in baseline IL-10 levels.
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Affiliation(s)
- Saira Rafaqat
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Azeem Azam
- Institute of Zoology, University of the Punjab, Lahore 54000, Pakistan
| | - Ramsha Hafeez
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Hamza Faseeh
- Department of Zoology, Govt. Islamia Graduate College Civil Lines, Lahore 54000, Pakistan
| | - Maria Tariq
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Muhammad Asif
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Amber Arshad
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Iqra Noshair
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
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Park SY, Park TG, Choi K, Kim KJ, Kim JY. The Impact of Pinus koraiensis Leaf Extract Consumption on Postprandial ApoB100 and Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled Trial in Healthy Participants Subjected to an Oral High-Fat Challenge. Nutrients 2024; 16:2864. [PMID: 39275181 PMCID: PMC11397107 DOI: 10.3390/nu16172864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/21/2024] [Accepted: 08/24/2024] [Indexed: 09/16/2024] Open
Abstract
Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.
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Affiliation(s)
- Soo-Yeon Park
- Department of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Tae Gwon Park
- Department of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Kwanyong Choi
- Department of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Kyeong Jin Kim
- Department of Nano Bio Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Ji Yeon Kim
- Department of Food Science and Biotechnology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
- Department of Nano Bio Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
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Seyiti Z, Yang L, Kasimujiang A, Dejite T, Shan XF, Gao XM. Predictive value of serum creatinine and total bilirubin for long-term death in patients with ischemic heart disease: A cohort study. PLoS One 2023; 18:e0294335. [PMID: 37971981 PMCID: PMC10653523 DOI: 10.1371/journal.pone.0294335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 10/30/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Ischemic heart disease (IHD) has a high mortality in the population. Although serum creatinine (Cr) and serum total bilirubin (TBil) are rapid and readily available biomarkers in routine blood tests, there is a lack of literature on the prognostic value of combined Cr and TBil tests for IHD. This study aimed to evaluate a combined equation based on Cr and TBil to predict the long-term risk of death in IHD and to find indicators sensitive to the prognosis of IHD patients. METHOD In this study, 2625 patients with IHD were included, and the combined value and combined equations of Cr and TBil were obtained by logistic regression analysis based on Cr and TBil collected at the time of admission. Patients were divided into four groups according to the quartiles of the combined value. COX proportional hazard regression model was used to analyze the risk factors for long-term death in IHD patients. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic effect of Cr, TBil and combined value on long-term death events. RESULTS Logistic regression analysis was performed for long-term death events with Cr and TBil as independent variables, and the logit regression model was Logit(P) = 0.0129×TBil+0.007×Cr-0.417. Multifactorial Cox regression analysis showed that high values of the equation were independent risk factors for long-term death events (all-cause death: HR 1.457, 95% CI 1.256-1.689, P<0.001; cardiovascular death: HR 1.452, 95% CI 1.244-1.695, P<0.001). Combined Cr and TBil value are more valuable in predicting long-term death (AUC: 0.609, 95% CI 0.587-0.630, P<0.001). CONCLUSION Combined Cr and TBil assay is superior to single biomarkers for predicting long-term death in patients with IHD. High values of the equation are independent predictors of long-term death and can be used to identify patients at high risk for IHD.
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Affiliation(s)
- Zulihuma Seyiti
- College of Pediatrics, Xinjiang Medical University, Urumqi, China
| | - Long Yang
- College of Pediatrics, Xinjiang Medical University, Urumqi, China
| | | | | | - Xue-Feng Shan
- Pediatric Cardiothoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology of the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi, China
| | - Xiao-Ming Gao
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology of the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi, China
- Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, China
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Singh K, Misra DP. Interleukin-10: Role in arterial wall homeostasis and dampening of inflammation in Takayasu arteritis. Int J Rheum Dis 2023; 26:1663-1666. [PMID: 37664962 DOI: 10.1111/1756-185x.14807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/16/2023] [Indexed: 09/05/2023]
Affiliation(s)
- Kritika Singh
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India
| | - Durga Prasanna Misra
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India
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Cui F, Mi H, Guan Y, Zhu Y, Wang R, Tian Y, Yang K, Zhang Y. Chronic intermittent hypobaric hypoxia ameliorates vascular reactivity through upregulating adiponectin expression of PVAT in metabolic syndrome rats. Can J Physiol Pharmacol 2023; 101:160-170. [PMID: 36716441 DOI: 10.1139/cjpp-2022-0252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Cumulating evidence demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had beneficial effects on the body. This study investigated the role of perivascular adipose tissue (PVAT) in ameliorating effect of CIHH on vascular reactivity by adiponectin in mesenteric artery of metabolic syndrome (MS) rats. Main methods: 6-week-old male Sprague-Dawley rats were randomly divided into four groups: control (CON), MS model, CIHH treatment, and MS + CIHH treatment group. The size of adipocytes in PVAT was measured by scanning electron microscopy. Serum adiponectin was measured. The microvessel recording technique was used to observe the effect of CIHH on contraction and relaxation in mesenteric artery rings. Also, the expressions of interleukin-1β, tumor necrosis factor-α, adiponectin, AdipoR1, AdipoR2, APPL1, and endothelial nitric oxide synthase (eNOS) were assayed by Western blotting. Key findings: in MS rats, adipocyte size increased, serum adiponectin decreased, contraction reaction increased while relaxation reaction decreased, the expression of pro-inflammatory cytokines was upregulated, while adiponectin was downregulated in PVAT, and the expressions of AdipoR1, AdipoR2, APPL, and phosphorylated-eNOS were downregulated in mesenteric artery. All aforementioned abnormalities of MS were ameliorated in MS + CIHH rats. We concluded that CIHH treatment improves vascular reactivity through upregulating adiponectin expression and downregulating pro-inflammatory cytokine expression of PVAT in MS rats.
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Affiliation(s)
- Fang Cui
- Department of Physiology, Hebei Medical University, Shijiazhuang 050017, P.R. China.,Department of Electron Microscope Laboratory, Hebei Medical University, Shijiazhuang 050017, P.R. China
| | - Haichao Mi
- Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, P.R. China
| | - Yue Guan
- Department of Physiology, Hebei Medical University, Shijiazhuang 050017, P.R. China
| | - Yan Zhu
- Department of Electron Microscope Laboratory, Hebei Medical University, Shijiazhuang 050017, P.R. China
| | - Ruotong Wang
- Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, P.R. China
| | - Yanming Tian
- Department of Physiology, Hebei Medical University, Shijiazhuang 050017, P.R. China
| | - Kaifan Yang
- College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, P.R. China
| | - Yi Zhang
- Department of Physiology, Hebei Medical University, Shijiazhuang 050017, P.R. China.,Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, P.R. China
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Freitas RAD, Lima VV, Bomfim GF, Giachini FRC. Interleukin-10 in the Vasculature: Pathophysiological Implications. Curr Vasc Pharmacol 2021; 20:230-243. [PMID: 34961448 DOI: 10.2174/1570161120666211227143459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/18/2021] [Accepted: 11/16/2021] [Indexed: 11/22/2022]
Abstract
Interleukin-10 (IL-10) is an important immunomodulatory cytokine, initially characterized as an anti-inflammatory agent released by immune cells during infectious and inflammatory processes. IL-10 exhibits biological functions that extend to the regulation of different intracellular signaling pathways directly associated with vascular function. This cytokine plays a vital role in vascular tone regulation through the change of important proteins involved in vasoconstriction and vasodilation. Numerous investigations covered here have shown that therapeutic strategies inducing IL-10 result in anti-inflammatory, anti-hypertrophic, antihyperplastic, anti-apoptotic and antihypertensive effects. This non-systematic review summarizes the modulating effects mediated by IL-10 in vascular tissue, particularly on vascular tone, and the intracellular pathway induced by this cytokine. We also highlight the advances in IL-10 manipulation as a therapeutic target in different cardiovascular pathophysiologies, including the physiological implications in animals and humans. Finally, the review illustrates current and potential future perspectives of the potential use of IL-10 in clinical trials, based on the clinical evidence.
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Affiliation(s)
| | - Victor Vitorino Lima
- Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças - Brazil
| | | | - Fernanda Regina Casagrande Giachini
- Institute of Biological Sciences, Federal University of Goias, Goiânia - Brazil.
- Institute of Biological Sciences and Health, Federal University of Mato Grosso, Barra do Garças - Brazil
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Soliman AM, Das S, Mahakkanukrauh P. Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review. Curr Med Chem 2021; 29:5522-5542. [PMID: 34488579 DOI: 10.2174/0929867328666210901122359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/01/2021] [Accepted: 07/23/2021] [Indexed: 11/22/2022]
Abstract
There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.
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Affiliation(s)
- Amro M Soliman
- Department of Biological Sciences-Physiology, Cell and Developmental Biology, University of Alberta, Edmonton, AB T6G 2R3. Canada
| | - Srijit Das
- Department of Human & Clinical Anatomy, College of Medicine & Health Sciences, Sultan Qaboos University, P.C. 123, Al Khoud, Muscat. Oman
| | - Pasuk Mahakkanukrauh
- Department of Anatomy & Excellence center of Osteology Research and Training, Cadaveric Surgical and Training Center, Chiang Mai University, Chiang Mai 50200. Thailand
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Pattarabanjird T, Li C, McNamara C. B Cells in Atherosclerosis: Mechanisms and Potential Clinical Applications. ACTA ACUST UNITED AC 2021; 6:546-563. [PMID: 34222726 PMCID: PMC8246059 DOI: 10.1016/j.jacbts.2021.01.006] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 01/05/2021] [Accepted: 01/05/2021] [Indexed: 12/17/2022]
Abstract
B cells regulate atherosclerotic plaque formation through production of antibodies and cytokines, and effects are subset specific (B1 and B2). Putative human atheroprotective B1 cells function similarly to murine B1 in their spontaneous IgM antibody production. However, marker strategies in identifying human and murine B1 are different. IgM antibody to oxidation specific epitopes produced by B1 cells associate with human coronary artery disease. Neoantigen immunization may be a promising strategy for atherosclerosis vaccine development, but further study to determine relevant antigens still need to be done. B-cell–targeted therapies, used in treating autoimmune diseases as well as lymphoid cancers, might have potential applications in treating cardiovascular diseases. Short- and long-term cardiovascular effects of these agents need to be assessed. Because atherosclerotic cardiovascular disease is a leading cause of death worldwide, understanding inflammatory processes underpinning its pathology is critical. B cells have been implicated as a key immune cell type in regulating atherosclerosis. B-cell effects, mediated by antibodies and cytokines, are subset specific. In this review, we focus on elaborating mechanisms underlying subtype-specific roles of B cells in atherosclerosis and discuss available human data implicating B cells in atherosclerosis. We further discuss potential B cell–linked therapeutic approaches, including immunization and B cell–targeted biologics. Given recent evidence strongly supporting a role for B cells in human atherosclerosis and the expansion of immunomodulatory agents that affect B-cell biology in clinical use and clinical trials for other disorders, it is important that the cardiovascular field be cognizant of potential beneficial or untoward effects of modulating B-cell activity on atherosclerosis.
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Key Words
- APRIL, A proliferation−inducing ligand
- ApoE, apolipoprotein E
- B-cell
- BAFF, B-cell–activating factor
- BAFFR, B-cell–activating factor receptor
- BCMA, B-cell maturation antigen
- BCR, B-cell receptor
- Breg, regulatory B cell
- CAD, coronary artery disease
- CTLA4, cytotoxic T-lymphocyte–associated protein 4
- CVD, cardiovascular disease
- CXCR4, C-X-C motif chemokine receptor 4
- GC, germinal center
- GITR, glucocorticoid-induced tumor necrosis factor receptor–related protein
- GITRL, glucocorticoid-induced tumor necrosis factor receptor–related protein ligand
- GM-CSF, granulocyte-macrophage colony–stimulating factor
- ICI, immune checkpoint inhibitor
- IFN, interferon
- IL, interleukin
- IVUS, intravascular ultrasound
- LDL, low-density lipoprotein
- LDLR, low-density lipoprotein receptor
- MDA-LDL, malondialdehyde-modified low-density lipoprotein
- MI, myocardial infarction
- OSE, oxidation-specific epitope
- OxLDL, oxidized low-density lipoprotein
- PC, phosphorylcholine
- PD-1, programmed cell death protein 1
- PD-L2, programmed death ligand 2
- PDL1, programmed death ligand 1
- RA, rheumatoid arthritis
- SLE, systemic lupus erythematosus
- TACI, transmembrane activator and CAML interactor
- TNF, tumor necrosis factor
- Treg, regulatory T cell
- atherosclerosis
- immunoglobulins
- mAb, monoclonal antibody
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Affiliation(s)
- Tanyaporn Pattarabanjird
- Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.,Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
| | - Cynthia Li
- Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Coleen McNamara
- Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.,Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
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Chen L, Holder R, Porter C, Shah Z. Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway. PLoS One 2021; 16:e0252816. [PMID: 34101754 PMCID: PMC8186764 DOI: 10.1371/journal.pone.0252816] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/21/2021] [Indexed: 01/10/2023] Open
Abstract
The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitamin D3 strongly attenuates doxorubicin-induced senescence and cell cycle arrest. We further show the protective effects of vitamin D3 are mediated by the upregulation of IL-10 and FOXO3a expression through fine modulation of pAMPKα/SIRT1/FOXO3a complex activity. These results have great significance in finding a target for mitigating doxorubicin-induced cardiovascular toxicity.
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Affiliation(s)
- Lei Chen
- Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Rachel Holder
- Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Charles Porter
- Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
| | - Zubair Shah
- Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
- * E-mail:
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Rehman K, Haider K, Jabeen K, Akash MSH. Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes. Rev Endocr Metab Disord 2020; 21:631-643. [PMID: 32125563 DOI: 10.1007/s11154-020-09549-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is a leading cause of deaths due to metabolic disorders in recent years. Molecular mechanisms involved in the initiation and development of IR and T2DM are multiples. The major factors include mitochondrial dysfunction which may cause incomplete fatty acid oxidation (FAO). Oleic acid upregulates the expression of genes causing FAO by deacetylation of PGC1α by PKA-dependent activation of SIRT1-PGC1α complex. Another potent factor for the development of IR and T2DM is endothelial dysfunction as damaged endothelium causes increased release of inflammatory mediators such as TNF-α, IL-6, IL-1β, sVCAM, sICAM, E-selectin and other proinflammatory cytokines. While, on the other hand, oleic acid has the ability to regulate E-selectin, and sICAM expression. Rest of the risk factors may include inflammation, β-cell dysfunction, oxidative stress, hormonal imbalance, apoptosis, and enzyme dysregulation. Here, we have highlighted how oleic acid regulates underlying causatives factors and hence, keeps surpassing effect in prevention and treatment of IR and T2DM. However, the percentage contribution of these factors in combating IR and ultimately averting T2DM is still debatable. Thus, because of its exceptional protective effect, it can be considered as an improved therapeutic agent in prophylaxis and/or treatment of IR and T2DM.
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Affiliation(s)
- Kanwal Rehman
- Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan.
| | - Kamran Haider
- Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan
| | - Komal Jabeen
- Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan
- Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
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12
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Cuthbert GA, Shaik F, Harrison MA, Ponnambalam S, Homer-Vanniasinkam S. Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease. Cells 2020; 9:cells9112453. [PMID: 33182772 PMCID: PMC7696859 DOI: 10.3390/cells9112453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/06/2020] [Accepted: 11/09/2020] [Indexed: 12/23/2022] Open
Abstract
The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment. In this review, we consider the main classes of SRs that are implicated in arterial disease. We consider how our understanding of SR-mediated recognition of diverse ligands, including modified lipid particles, lipids, and carbohydrates, has enabled us to better target SR-linked functionality in disease. We also link clinical studies on vascular disease to our current understanding of SR biology and highlight potential areas that are relevant to cardiovascular disease management and therapy.
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Affiliation(s)
- Gary A. Cuthbert
- Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK;
- Correspondence: ; Tel.:+44 113 3433007
| | - Faheem Shaik
- School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, UK; (F.S.); (S.P.)
| | | | - Sreenivasan Ponnambalam
- School of Molecular & Cellular Biology, University of Leeds, Leeds LS2 9JT, UK; (F.S.); (S.P.)
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13
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Effects of Altered Levels of Pro- and Anti-Inflammatory Mediators on Locations of In-Stent Reocclusions in Elderly Patients. Mediators Inflamm 2020; 2020:1719279. [PMID: 33029103 PMCID: PMC7530477 DOI: 10.1155/2020/1719279] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 02/08/2023] Open
Abstract
Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 β (IL-1 β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 β, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations.
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14
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Lim Y, Hwang W, Kim JY, Lee CH, Kim YJ, Lee D, Kwon O. Synergistic mechanisms of Sanghuang-Danshen phytochemicals on postprandial vascular dysfunction in healthy subjects: A network biology approach based on a clinical trial. Sci Rep 2019; 9:9746. [PMID: 31278329 PMCID: PMC6611899 DOI: 10.1038/s41598-019-46289-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 06/26/2019] [Indexed: 11/13/2022] Open
Abstract
With the increased risk of cardiovascular disease, the use of botanicals for vascular endothelial dysfunction has intensified. Here, we explored the synergistic mechanisms of Sanghuang–Danshen (SD) phytochemicals on the homeostatic protection against high-fat-induced vascular dysfunction in healthy subjects, using a network biology approach, based on a randomised crossover clinical trial. Seventeen differential markers identified in blood samples taken at 0, 3 and 6 h post-treatment, together with 12SD phytochemicals, were mapped onto the network platform, termed the context-oriented directed associations. The resulting vascular sub-networks illustrated associations between 10 phytochemicals with 32 targets implicated in 143 metabolic/signalling pathways. The three key events included adhesion molecule production (ellagic acid, fumaric acid and cryptotanshinone; VCAM-1, ICAM-1 and PLA2G2A; fatty acid metabolism), platelet activation (ellagic acid, protocatechuic acid and tanshinone IIA; VEGFA, APAF1 and ATF3; mTOR, p53, Rap1 and VEGF signalling pathways) and endothelial inflammation (all phytochemicals, except cryptotanshinone; 29 targets, including TP53 and CASP3; MAPK and PI3K-Akt signalling pathways, among others). Our collective findings demonstrate a potential of SD to protect unintended risks of vascular dysfunction in healthy subjects, providing a deeper understanding of the complicated synergistic mechanisms of signature phytochemicals in SD.
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Affiliation(s)
- Yeni Lim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Woochang Hwang
- Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea
| | - Ji Yeon Kim
- Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea
| | - Choong Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea
| | - Yong-Jae Kim
- Department of Neurology, Ewha Womans University School of Medicine, Seoul, 07985, Republic of Korea
| | - Doheon Lee
- Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea.
| | - Oran Kwon
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Republic of Korea.
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15
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Zhang T, Li Q, Wang L, Li G. Expression variations and clinical significance of MMP-1, MMP-2 and inflammatory factors in serum of patients with deep venous thrombosis of lower extremity. Exp Ther Med 2018; 17:181-186. [PMID: 30651780 PMCID: PMC6307431 DOI: 10.3892/etm.2018.6922] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 10/24/2018] [Indexed: 11/25/2022] Open
Abstract
Expression levels and clinical significance of matrix metalloproteinase-1 (MMP1), MMP-2 and inflammatory factors in the serum of patients with deep venous thrombosis (DVT) of lower extremity were investigated. Fifty untreated DVT patients were selected as the DVT group, and 50 patients undergoing health examination were enrolled as the normal control group. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of MMP-1, MMP-2, interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in the serum. Western blotting was adopted to detect the expression levels of MMP-1 and MMP-2 proteins. Fluorescent reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to examine the messenger ribonucleic acid (mRNA) expression levels. Moreover, the circumferences of the patients were measured. The difference between the circumference of affected extremity and unaffected extremity was calculated. Correlation analysis was conducted separately for the levels of serum MMP-1, MMP-2, IL-6, IL-8 and TNF-α of patients in the DVT group. In the DVT group, the levels of MMP-1, MMP-2, IL-6, IL-8, and TNF-α at 7 days after treatment were significantly lower than those before treatment (P<0.01). Compared with that before treatment, the circumference difference of the affected and unaffected extremities of the patients was reduced at 7 days after treatment (P<0.01). The levels of IL-6, IL-8 and TNF-α were positively correlated with the levels of MMP-1 and MMP-2, respectively in the DVT group (P<0.05 or P<0.01). MMP-1, MMP-2 and inflammatory factors play an important role in the occurrence and development of DVT, of which the levels of IL-6, IL-8 and TNF-α are positively correlated with the levels of MMP-1 and MMP-2, respectively. Therefore, monitoring the concentration of MMP-1, MMP-2 and inflammatory factors is of significant value for the diagnosis, progression and judgement of treatment effect of DVT in clinical practice.
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Affiliation(s)
- Tangshan Zhang
- Department of Vascular Surgery, People's Hospital of Jiyang, Jinan, Shandong 251400, P.R. China
| | - Qiang Li
- Department of Critical Care Medicine, People's Hospital of Jiyang, Jinan, Shandong 251400, P.R. China
| | - Lijuan Wang
- Operating Room, People's Hospital of Jiyang, Jinan, Shandong 251400, P.R. China
| | - Guangxin Li
- Department of Vascular Surgery, Qianfoshan Hospital, Jinan, Shandong 251400, P.R. China
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16
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Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol 2018; 9:586. [PMID: 29686666 PMCID: PMC5900450 DOI: 10.3389/fimmu.2018.00586] [Citation(s) in RCA: 783] [Impact Index Per Article: 111.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 03/08/2018] [Indexed: 12/11/2022] Open
Abstract
Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.
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Affiliation(s)
- Irene Maeve Rea
- School of Medicine, Dentistry and Biomedical Science, Queens University Belfast, Belfast, United Kingdom
- Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, C-TRIC Building, Altnagelvin Area Hospital, Londonderry, United Kingdom
- Care of Elderly Medicine, Belfast Health and Social Care Trust, Belfast, United Kingdom
| | - David S. Gibson
- Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, C-TRIC Building, Altnagelvin Area Hospital, Londonderry, United Kingdom
| | - Victoria McGilligan
- Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, C-TRIC Building, Altnagelvin Area Hospital, Londonderry, United Kingdom
| | - Susan E. McNerlan
- Regional Genetics Service, Belfast Health and Social Care Trust, Belfast, United Kingdom
| | - H. Denis Alexander
- Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, C-TRIC Building, Altnagelvin Area Hospital, Londonderry, United Kingdom
| | - Owen A. Ross
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
- Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, United States
- School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
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17
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Alikhah A, Pahlevan Kakhki M, Ahmadi A, Dehghanzad R, Boroumand MA, Behmanesh M. The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus. J Diabetes Complications 2018; 32:258-265. [PMID: 29398326 DOI: 10.1016/j.jdiacomp.2017.12.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 11/09/2017] [Accepted: 12/02/2017] [Indexed: 01/05/2023]
Abstract
AIMS Coronary artery disease (CAD) can be classified as an inflammatory disease, which affected by type 2 diabetes mellitus (T2DM). Elevated levels of many inflammatory molecules were found in the serum of patients with CAD. STAT3 molecule as a transcription factor plays an important role in the cytokines expression. Here, we examined the expression levels of STAT3 and its important regulatory genes lnc-DC and SOCS1, in patients with CAD and T2DM. METHODS Blood samples were obtained from 37 CAD+ and 36 CAD- patients. These patients were enrolled in this study based on angiography findings and categorized based on T2DM status. The expression levels of STAT3, lnc-DC and SOCS1 genes were examined with Real time PCR method. RESULTS A significant increase was observed in expression of STAT3 and lnc-DC genes but not SOCS1 in CAD+ versus CAD- patients. These results replicated partially in some groups categorized based on T2DM and CAD status. However, severity of CAD had no effect on expressions of these genes. Moreover, we found some significant correlations between expressions of lnc-DC with SOCS1 and STAT3, which confirmed by in silico analysis. CONCLUSION Our results shed further light to the inflammatory aspects of CAD and T2DM with emphasis to JAK/STAT pathway and the regulatory role of long non-coding RNAs in the physiopathology of these diseases.
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Affiliation(s)
- Asieh Alikhah
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Majid Pahlevan Kakhki
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Amirhossain Ahmadi
- Department of Biology, Faculty of Basic Sciences, Persian Gulf University, Bushehr, Iran
| | - Reyhaneh Dehghanzad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | | | - Mehrdad Behmanesh
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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18
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Lim Y, Kwon O, Kim JY. The Model for Evaluation on Blood Flow of Functional Food in Human Intervention Study. J Lipid Atheroscler 2018. [DOI: 10.12997/jla.2018.7.2.88] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Yeni Lim
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea
| | - Oran Kwon
- Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea
| | - Ji Yeon Kim
- Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul, Korea
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19
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Xiong YS, Wu AL, Mu D, Yu J, Zeng P, Sun Y, Xiong J. Inhibition of siglec-1 by lentivirus mediated small interfering RNA attenuates atherogenesis in apoE-deficient mice. Clin Immunol 2016; 174:32-40. [PMID: 27871915 DOI: 10.1016/j.clim.2016.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 11/13/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND Siglec-1 is highly expressed on circulating monocytes and plaque macrophages in atherosclerotic patients, but the exact role of Siglec-1 in atherosclerosis has not been elucidated. METHODS Lentiviral vector containing small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv-shNC) were injected intravenously into 6-week old Apoe-/- mice. Then onset of atherosclerosis was observed. RESULTS Siglec-1 was highly expressed in aortic plaques and it can be down-regulated by Lv-shSiglec-1 injection. The plaque area and serum pro-inflammatory cytokine (IL-1β, IL-6, TNF-α and IL-17A) levels in Lv-shSiglec-1 mice were significantly lower than Lv-shNC mice, whereas IL-10 was higher. Moreover, plaque macrophages accumulation in aortic wall in Lv-shSiglec-1 mice was diminish, partly by decreased secretion of MCP-1/CXCL2 and CCR2/CXCR2 of aortas and monocytes, respectively. Furthermore, silencing of Siglec-1 can attenuate oxLDL uptake by peritoneal macrophages. CONCLUSIONS Inhibition of Siglec-1 can prevent atherosclerotic lesion formation by suppress monocytes-endothelial cells adhesion and macrophages accumulation.
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Affiliation(s)
- Yi-Song Xiong
- Department of Laboratory Medicine, Chengdu Military General Hospital, Chengdu, China.
| | - Ai-Lin Wu
- Department of Laboratory Medicine, Chengdu Military General Hospital, Chengdu, China
| | - Dong Mu
- Department of Gastroenterology, Chengdu Military General Hospital, Chengdu, China
| | - Juan Yu
- Center of Laboratory Medicine, Affiliated Hospital, Nantong University, Nantong, China; Institute of Public Health, Nantong University, Nantong, China
| | - Ping Zeng
- Department of Laboratory Medicine, Chengdu Military General Hospital, Chengdu, China
| | - Yi Sun
- Department of Laboratory Diagnostics, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jie Xiong
- Department of Laboratory Medicine, Chengdu Military General Hospital, Chengdu, China.
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20
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Honda A, Tahara N, Nitta Y, Tahara A, Igata S, Bekki M, Nakamura T, Sugiyama Y, Kaida H, Kurata S, Fujimoto K, Abe T, Enomoto M, Adachi H, Narula J, Yamagishi SI, Fukumoto Y. Vascular Inflammation Evaluated by [
18
F]-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Is Associated With Endothelial Dysfunction. Arterioscler Thromb Vasc Biol 2016; 36:1980-8. [DOI: 10.1161/atvbaha.116.307293] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 06/23/2016] [Indexed: 01/07/2023]
Abstract
Objective—
Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [
18
F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging.
Approach and Results—
We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [
18
F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Δ%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Δ%FMD and ΔTBR; ΔTBR was a sole independent associate of Δ%FMD in hypertensive patients (
r
=−0.558;
P
<0.001).
Conclusions—
The present study showed that vascular inflammation in the carotid arteries evaluated by [
18
F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.
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Affiliation(s)
- Akihiro Honda
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Nobuhiro Tahara
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Yoshikazu Nitta
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Atsuko Tahara
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Sachiyo Igata
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Munehisa Bekki
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Tomohisa Nakamura
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Yoichi Sugiyama
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Hayato Kaida
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Seiji Kurata
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Kiminori Fujimoto
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Toshi Abe
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Mika Enomoto
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Hisashi Adachi
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Jagat Narula
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Sho-ichi Yamagishi
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
| | - Yoshihiro Fukumoto
- From the Division of Cardiovascular Medicine, Department of Medicine (A.H., N.T., Y.N., A.T., S.I., M.B., T.N., Y.S., M.E., H.A., Y.F.), Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications (S-i.Y.), and Department of Radiology (H.K., S.K., K.F., T.A.), Kurume University School of Medicine, Kurume, Japan; and Department of Cardiology, Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (J.N.)
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Sasaki H, Hirai K, Martins CM, Furusho H, Battaglino R, Hashimoto K. Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders. Curr Pharm Des 2016; 22:2204-15. [PMID: 26881444 PMCID: PMC4856634 DOI: 10.2174/1381612822666160216145107] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 02/15/2016] [Indexed: 12/25/2022]
Abstract
BACKGROUND Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a "metabolically-triggered" low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. METHOD We have reviewed >200 articles to discuss the interrelationship between periapical lesions and metabolic disorders including type 2 diabetes mellitus, hypertension, and non-alcoholic fatty liver diseases (NAFLD), and their common pathological background in immunology/osteoimmunology and cytokine biology. RESULTS An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non-alcoholic steatohepatitis. CONCLUSION Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship.
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Affiliation(s)
- Hajime Sasaki
- Department of Immunology & Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02494, U.S.A.
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22
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Babbitt DM, Kim JS, Forrester SJ, Brown MD, Park JY. Effect of Interleukin-10 and Laminar Shear Stress on Endothelial Nitric Oxide Synthase and Nitric Oxide in African American Human Umbilical Vein Endothelial Cells. Ethn Dis 2015; 25:413-8. [PMID: 26674844 DOI: 10.18865/ed.25.4.413] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND African Americans have a predisposition to heightened systemic inflammation and a high prevalence of hypertension. OBJECTIVE The purpose of this study was to evaluate the influence of interleukin-10 (IL-10) and laminar shear stress (LSS) on African American endothelial cells by measuring total endothelial nitric oxide synthase (eNOS) protein expression and its phosphorylated form (p-eNOS) at Serine 1177, and nitric oxide (NO) levels, in response to IL-10 incubation and high physiological levels of LSS, used as an in vitro mimetic for aerobic exercise training (AEXT). DESIGN Human umbilical vein endothelial cells (HUVEC) from an African American donor were cultured. The experimental conditions included Static, Static with IL-10 Incubation, LSS at 20 dynes/cm², and LSS at 20 dynes/cm² with IL-10 Incubation. Western blotting was used to measure eNOS and p-eNOS protein expression in the cells. A modified Griess assay was used to measure NO metabolites in the cell culture media. RESULTS There were significant increases in p-eNOS, eNOS, and NO in the LSS at 20 dynes/cm² and LSS at 20 dynes/cm² with IL-10 Incubation experimental conditions when compared to the Static experimental condition. There were no other statistically significant differences demonstrating that IL-10 did not have an additive effect on eNOS activity in our study. CONCLUSION The significant increases in p-eNOS, eNOS, and NO as a result of LSS in African American HUVECs suggest that AEXT may be a viable, nonpharmacologic method to improve vascular inflammation status and vasodilation, and thereby contribute to hypertension reduction in the African American population.
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Affiliation(s)
| | - Ji-Seok Kim
- 2. Department of Kinesiology, Temple University
| | | | - Michael D Brown
- 3. Vascular Health Laboratory, Department of Kinesiology & Nutrition, University of Illinois at Chicago
| | - Joon-Young Park
- 2. Department of Kinesiology, Temple University ; 4.Cardiovascular Research Center, Temple University School of Medicine
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Rodrigues KF, Pietrani NT, Sandrim VC, Vieira CMAF, Fernandes AP, Bosco AA, Gomes KB. Association of a Large Panel of Cytokine Gene Polymorphisms with Complications and Comorbidities in Type 2 Diabetes Patients. J Diabetes Res 2015; 2015:605965. [PMID: 26064986 PMCID: PMC4438177 DOI: 10.1155/2015/605965] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 04/09/2015] [Accepted: 04/15/2015] [Indexed: 12/12/2022] Open
Abstract
AIMS The polymorphisms of pro- and anti-inflammatory cytokines may be involved in type 2 diabetes (T2D) pathogenesis and its complications. METHODS We investigated in 102 T2D patients the association of the cytokine polymorphisms in the TNF-α, IL-10, IL-6, TGF-β1, and IFN-γ genes with the T2D microvascular complications and comorbidities (hypertension, dyslipidemia, and obesity). Cytokine genotypes were determined by PCR using Cytokine Genotyping Tray kit. RESULTS Diabetic retinopathy was associated with GG genotype and G allele in TGF-β1 codon 25C/G polymorphism (p = 0.004 and p = 0.018) and the nephropathy was associated the lower frequency of GG genotype in IL-10 -1082G/A polymorphism (p = 0.049). Hypertension was associated with the CC genotype and C allele for IL-10 -592C/A polymorphism (p = 0.013 and p = 0.009) and higher frequencies of T (p = 0.047) and C (p = 0.033) alleles of the TGF-β1 codon 10T/C and IL-10 -819T/C polymorphisms, respectively. The TGF-β1 codon 10T/C polymorphism was associated with the BMI groups (p = 0.026): the CC genotype was more frequent in the group with BMI < 25 Kg/m(2), while the TC genotype was more frequent in the group with BMI = 30 Kg/m(2). CONCLUSIONS Our findings suggest that TGF-β1 and IL-10 polymorphisms are involved in complications and comorbidities in T2D patients.
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Affiliation(s)
- K. F. Rodrigues
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - N. T. Pietrani
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - V. C. Sandrim
- Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu, SP, Brazil
| | - C. M. A. F. Vieira
- Instituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - A. P. Fernandes
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, No. 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil
| | - A. A. Bosco
- Instituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
| | - K. B. Gomes
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, No. 6627, Pampulha, 31270-901 Belo Horizonte, MG, Brazil
- *K. B. Gomes:
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Shao Y, Cheng Z, Li X, Chernaya V, Wang H, Yang XF. Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction--a novel mechanism for maintaining vascular function. J Hematol Oncol 2014; 7:80. [PMID: 25387998 PMCID: PMC4236671 DOI: 10.1186/s13045-014-0080-6] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Accepted: 10/13/2014] [Indexed: 12/14/2022] Open
Abstract
Endothelial dysfunction is a pathological status of the vascular system, which can be broadly defined as an imbalance between endothelium-dependent vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the progression of many pathological processes including atherosclerosis, type II diabetes and hypertension. Previous reports have demonstrated that pro-inflammatory/immunoeffector cytokines significantly promote endothelial dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines have recently been identified such as interleukin (IL)-35. However, the effects of anti-inflammatory cytokines on endothelial dysfunction have received much less attention. In this analytical review, we focus on the recent progress attained in characterizing the direct and indirect effects of anti-inflammatory/immunosuppressive cytokines in the inhibition of endothelial dysfunction. Our analyses are not only limited to the importance of endothelial dysfunction in cardiovascular disease progression, but also expand into the molecular mechanisms and pathways underlying the inhibition of endothelial dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.
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Affiliation(s)
- Ying Shao
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA.
| | - Zhongjian Cheng
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA.
| | - Xinyuan Li
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA.
| | - Valeria Chernaya
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA.
| | - Hong Wang
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA.
| | - Xiao-feng Yang
- Department of Pharmacology, Center for Metabolic Disease Research and Cardiovascular Research Center, Temple University School of Medicine, MERB 1059, 3500 North Broad Street, Philadelphia, PA, 19140, USA. .,Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, 19140, USA.
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25
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Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement. Atherosclerosis 2014; 237:784-9. [PMID: 25463121 DOI: 10.1016/j.atherosclerosis.2014.10.096] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2014] [Revised: 10/05/2014] [Accepted: 10/17/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent. METHODS Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement. RESULTS Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement. CONCLUSION This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.
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26
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Yamak M, Demir S, Gursu M, Ozturk S, Sumnu A, Cebeci E, Ozkan O, Karadag S, Sakci E, Kural A, Koldas M, Sar F. The Relationship between Plasma Soluble Tnf-like Weak Inducer of Apoptosis Level and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus. EUR J INFLAMM 2014. [DOI: 10.1177/1721727x1401200305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a member of the TNF super family with many biological activities. There is a limited number of studies on the role of sTWEAK in chronic kidney disease. We aimed in this study to examine the relation of sTWEAK with albuminuria and inflammatory markers in patients with type 2 diabetes mellitus (DM). One hundred and eighteen diabetic patients with varying levels of albuminuria were included. Group 1 comprised patients with albuminuria less than 30 mg/day, while Group 2 and Group 3 were composed of patients with albuminuria between 30–300 mg/day or more than 300 mg/day, respectively. Groups were compared for sTWEAK levels besides demographic, clinical and biochemical data. There was no difference between groups regarding sTWEAK and TNF-α levels. IL-1 levels in Group 1 were higher than in Group 3. hsCRP levels were significantly higher in Group 3 compared to other groups. Use of a renin angiotensin system blocker did not have any effect on sTWEAK, TNF-α and hsCRP levels, while IL-1 level was significantly lower in patients using a renin angiotensin blocker. A statistically significant positive correlation was detected between sTWEAK and IL-1 levels (r=0.245; p=0.008). The groups were found to be similar regarding sTWEAK and TNF-α level. This finding may be interpreted as there being no effect of proteinuria on sTWEAK levels. But the close correlation between proteinuria and IL-1, and between IL-1 and sTWEAK may be a clue for an indirect relationship. Lack of difference between groups regarding sTWEAK levels may be due to involvement of patients with GFR more than 60 ml/minute only.
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Affiliation(s)
- M. Yamak
- Department of Internal Medicine, Haseki Training and Research Hospital, Istanbul, Turkey
| | - S. Demir
- Department of Internal Medicine, Haseki Training and Research Hospital, Istanbul, Turkey
| | - M. Gursu
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - S. Ozturk
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - A. Sumnu
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - E. Cebeci
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - O. Ozkan
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - S. Karadag
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - E. Sakci
- Department of Internal Medicine, Haseki Training and Research Hospital, Istanbul, Turkey
| | - A. Kural
- Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey
| | - M. Koldas
- Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey
| | - F. Sar
- Department of Nephrology, Haseki Training and Research Hospital, Istanbul, Turkey
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Schindler TH, Quercioli A, Valenta I, Ambrosio G, Wahl RL, Dilsizian V. Quantitative Assessment of Myocardial Blood Flow—Clinical and Research Applications. Semin Nucl Med 2014; 44:274-93. [DOI: 10.1053/j.semnuclmed.2014.04.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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He F, Teng X, Gu H, Liu H, Zhou Z, Zhao Y, Hu S, Zheng Z. Interleukin-6 receptor rs7529229 T/C polymorphism is associated with left main coronary artery disease phenotype in a Chinese population. Int J Mol Sci 2014; 15:5623-33. [PMID: 24699044 PMCID: PMC4013585 DOI: 10.3390/ijms15045623] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 03/15/2014] [Accepted: 03/20/2014] [Indexed: 02/08/2023] Open
Abstract
Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD). In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ligation detection reaction (LDR) method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR)=1.46, 95% confidence interval (CI)=1.02-2.11, p=0.042; CC+TC vs. TT, adjusted OR=1.31, 95% CI=1.02-1.69, p=0.037). None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.
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Affiliation(s)
- Feng He
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Xiao Teng
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Haiyong Gu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.
| | - Hanning Liu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Zhou Zhou
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Yan Zhao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Shengshou Hu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
| | - Zhe Zheng
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
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The TGF-B1 and IL-10 gene polymorphisms are associated with risk of developing silent myocardial ischemia in the diabetic patients. Immunol Lett 2013; 156:18-22. [DOI: 10.1016/j.imlet.2013.09.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Revised: 09/11/2013] [Accepted: 09/12/2013] [Indexed: 01/27/2023]
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Endothelial activation microparticles and inflammation status improve with exercise training in african americans. Int J Hypertens 2013; 2013:538017. [PMID: 23691280 PMCID: PMC3652180 DOI: 10.1155/2013/538017] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Accepted: 02/10/2013] [Indexed: 02/07/2023] Open
Abstract
African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change in VO2 max significantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans.
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Obesity Modulates the Immune Response to Oxidized LDL in Hypertensive Patients. Cell Biochem Biophys 2013; 67:1451-60. [DOI: 10.1007/s12013-013-9585-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Bzowska M, Nogieć A, Skrzeczyńska-Moncznik J, Mickowska B, Guzik K, Pryjma J. Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: a new aspect of pathogen-accelerated atherosclerosis. Inflammation 2013; 35:1567-84. [PMID: 22556042 PMCID: PMC3397235 DOI: 10.1007/s10753-012-9472-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
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Affiliation(s)
- Małgorzata Bzowska
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Anna Nogieć
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Joanna Skrzeczyńska-Moncznik
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Barbara Mickowska
- Malopolska Centre of Food Monitoring and Certification, Faculty of Food Technology, Agricultural University, Balicka 122, 30-149 Kraków, Poland
| | - Krzysztof Guzik
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Juliusz Pryjma
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
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Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: a new aspect of pathogen-accelerated atherosclerosis. Inflammation 2013. [PMID: 22556042 DOI: 10.1007/s110753-012-9472-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
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Perry HM, Bender TP, McNamara CA. B cell subsets in atherosclerosis. Front Immunol 2012; 3:373. [PMID: 23248624 PMCID: PMC3518786 DOI: 10.3389/fimmu.2012.00373] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Accepted: 11/21/2012] [Indexed: 12/21/2022] Open
Abstract
Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis by secretion of natural IgM antibodies. Conventional B-2 B cells can promote atherosclerosis through less clearly defined mechanism that may involve CD4 T cells. Yet, there may be other populations of B cells within these subsets with different phenotypes altering their impact on atherosclerosis. Additionally, the role of B cell subsets in atherosclerosis may depend on their environmental niche and/or the stage of atherogenesis. This review will highlight key findings in the evolving field of B cells and atherosclerosis and touch on the potential and importance of translating these findings to human disease.
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Affiliation(s)
- Heather M Perry
- Department of Pathology, University of Virginia Charlottesville, VA, USA ; Cardiovascular Research Center, University of Virginia Health System Charlottesville, VA, USA
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Coronary Vasomotor Control in Obesity and Morbid Obesity. JACC Cardiovasc Imaging 2012; 5:805-15. [PMID: 22897994 DOI: 10.1016/j.jcmg.2012.01.020] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 01/24/2012] [Accepted: 01/26/2012] [Indexed: 11/23/2022]
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Abstract
BNP (B-type natriuretic peptide) has been reported to be elevated in preclinical states of vascular damage. To elucidate the relationship between plasma BNP and endothelial function, we have investigated the relationship between BNP and endothelial function in a cohort of subjects comprising healthy subjects as well as at-risk subjects with cardiovascular risk factors. To also clarify the relative contribution of different biological pathways to the individual variation in endothelial function, we have examined the relationship between a panel of multiple biomarkers and endothelial function. A total of 70 subjects were studied (mean age, 58.1±4.6 years; 27% had a history of hypertension and 18% had a history of hypercholesterolaemia). Endothelium-dependent vasodilatation was evaluated by the invasive ACH (acetylcholine)-induced forearm vasodilatation technique. A panel of biomarkers of biological pathways was measured: BNP, haemostatic factors PAI-1 (plasminogen-activator inhibitor 1) and tPA (tissue plasminogen activator), inflammatory markers, including cytokines [hs-CRP (high sensitive C-reactive protein), IL (interleukin)-6, IL-8, IL-18, TNFα (tumour necrosis factor α) and MPO (myeloperoxidase] and soluble adhesion molecules [E-selectin and sCD40 (soluble CD40)]. The median BNP level in the study population was 26.9 pg/ml. Multivariate regression analyses show that age, the total cholesterol/HDL (high-density lipoprotein) ratio, glucose and BNP were independent predictors of endothelial function, and BNP remained an independent predictor (P=0.009) in a binary logistic regression analysis using FBF (forearm blood flow) as a dichotomous variable based on the median value. None of the other plasma biomarkers was independently related to ACH-mediated vasodilatation. In a strategy using several biomarkers to relate to endothelial function, plasma BNP was found to be an independent predictor of endothelial function as assessed by endothelium-dependent vasodilatation in response to ACH.
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Association of promoter region single nucleotide polymorphisms at positions −819C/T and −592C/A of interleukin 10 gene with ischemic heart disease. Inflamm Res 2012; 61:899-905. [DOI: 10.1007/s00011-012-0482-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2011] [Accepted: 04/19/2012] [Indexed: 02/01/2023] Open
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Yang H, Chen S, Tang Y, Dai Y. Interleukin-10 down-regulates oxLDL induced expression of scavenger receptor A and Bak-1 in macrophages derived from THP-1 cells. Arch Biochem Biophys 2011; 512:30-7. [DOI: 10.1016/j.abb.2011.05.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2011] [Revised: 05/01/2011] [Accepted: 05/23/2011] [Indexed: 01/09/2023]
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Joviliano EE, Piccinato CE, Dellalibera-Joviliano R, Moriya T, Évora PR. Inflammatory Markers and Restenosis in Peripheral Percutaneous Angioplasty With Intravascular Stenting: Current Concepts. Ann Vasc Surg 2011; 25:846-55. [DOI: 10.1016/j.avsg.2011.02.026] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2010] [Revised: 12/16/2010] [Accepted: 02/21/2011] [Indexed: 11/25/2022]
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Kokjohn TA, Van Vickle GD, Maarouf CL, Kalback WM, Hunter JM, Daugs ID, Luehrs DC, Lopez J, Brune D, Sue LI, Beach TG, Castaño EM, Roher AE. Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets. Biochim Biophys Acta Mol Basis Dis 2011; 1812:1508-14. [PMID: 21784149 DOI: 10.1016/j.bbadis.2011.07.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Revised: 06/27/2011] [Accepted: 07/05/2011] [Indexed: 01/23/2023]
Abstract
Amyloid-β (Aβ) peptides are intimately involved in the inflammatory pathology of atherosclerotic vascular disease (AVD) and Alzheimer's disease (AD). Although substantial amounts of these peptides are produced in the periphery, their role and significance to vascular disease outside the brain requires further investigation. Amyloid-β peptides present in the walls of human aorta atherosclerotic lesions as well as activated and non-activated human platelets were isolated using sequential size-exclusion columns and HPLC reverse-phase methods. The Aβ peptide isolates were quantified by ELISA and structurally analyzed using MALDI-TOF mass spectrometry procedures. Our experiments revealed that both aorta and platelets contained Aβ peptides, predominately Aβ40. The source of the Aβ pool in aortic atherosclerosis lesions is probably the activated platelets and/or vascular wall cells expressing APP/PN2. Significant levels of Aβ42 are present in the plasma, suggesting that this reservoir makes a minor contribution to atherosclerotic plaques. Our data reveal that although aortic atherosclerosis and AD cerebrovascular amyloidosis exhibit clearly divergent end-stage manifestations, both vascular diseases share some key pathophysiological promoting elements and pathways. Whether they happen to be deposited in vessels of the central nervous system or atherosclerotic plaques in the periphery, Aβ peptides may promote and perhaps synergize chronic inflammatory processes which culminate in the degeneration, malfunction and ultimate destruction of arterial walls.
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Affiliation(s)
- Tyler A Kokjohn
- The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ 85351, USA
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Alleles and haplotypes of the interleukin 10 gene polymorphisms are associated with risk of developing acute coronary syndrome in Mexican patients. Cytokine 2011; 55:29-33. [DOI: 10.1016/j.cyto.2011.03.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2010] [Revised: 02/11/2011] [Accepted: 03/18/2011] [Indexed: 11/18/2022]
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Araña Rosaínz MDJ, Ojeda MO, Acosta JR, Elías-Calles LC, González NO, Herrera OT, García Álvarez CT, Rodríguez EM, Báez ME, Seijas EÁ, Valdés RF. Imbalanced low-grade inflammation and endothelial activation in patients with type 2 diabetes mellitus and erectile dysfunction. J Sex Med 2011; 8:2017-30. [PMID: 21554550 DOI: 10.1111/j.1743-6109.2011.02277.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Erectile dysfunction (ED) is highly prevalent among type 2 diabetes mellitus patients (T2DM). Although a link among systemic inflammation, endothelial dysfunction, and ED is described in clinical situations mainly related with coronary heart disease (CHD) risk, evidences of this link in T2DM patients are rather limited. AIMS To evaluate the association between endothelial dysfunction and balance of pro-/anti-inflammatory mediators with ED presence and severity in T2DM. METHODS We conducted a cross-sectional study of 190 T2DM patients without symptomatic CHD, 150 out of them with ED and 40 without ED. Serum levels of E-selectin, intercellular adhesion molecule-1, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 were measured using specific enzyme-linked immunosorbent assays (ELISAs). ED presence and severity were tested by the five-item version of the International Index of Erectile Function questionnaire. MAIN OUTCOME MEASURES Differences in circulating levels of endothelial dysfunction (ICAM-1, E-selectin) and inflammatory/anti-inflammatory (TNF-α, IL-10, TNF-α : IL-10 ratio) markers between T2DM patients with and without ED, and assessment of biomarkers ED predictive value while adjusting for other known ED risk factors. RESULTS Patients with ED were older and had longer duration of diabetes than patients without ED. E-selectin serum levels were significantly increased, while IL-10 were lower in patients with ED; because TNF-α levels tend to be higher, TNF-α : IL-10 ratio was more elevated in ED patients. No significant differences of ICAM-1 levels were observed between study groups. Endothelial activation markers and TNF-α, as well as diabetes duration, were negatively correlated with erectile function. On multivariate analysis including age, duration of diabetes, insulin treatment, hypertension, insulin resistance, fair-to-poor glycemic control, and metabolic syndrome, increments in E-selectin levels and TNF-α : IL-10 ratio predicted independently ED presence, while IL-10 increases were associated with lower risk of ED in T2DM patients. CONCLUSIONS ED in T2DM patients without symptomatic CHD is associated with systemic endothelial dysfunction and a predominant, imbalanced low-grade inflammatory response.
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Brunetti ND, Munno I, Pellegrino PL, Ruggero V, Correale M, De Gennaro L, Cuculo A, Campanale EG, Di Biase M. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events. Inflammation 2011; 34:58-66. [PMID: 20405189 DOI: 10.1007/s10753-010-9208-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.
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Du L, Dronadula N, Tanaka S, Dichek DA. Helper-dependent adenoviral vector achieves prolonged, stable expression of interleukin-10 in rabbit carotid arteries but does not limit early atherogenesis. Hum Gene Ther 2011; 22:959-68. [PMID: 21198399 DOI: 10.1089/hum.2010.175] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Vascular gene therapy could potentially complement or replace current therapies for human atherosclerosis, while avoiding their side effects. However, development of vascular gene therapy is limited by lack of a useful vector. Helper-dependent adenovirus (HDAd) shows promise to overcome this barrier because, unlike first-generation adenovirus, HDAd achieves durable transgene expression in the artery wall with minimal inflammation. To begin to test whether HDAd, delivered to the artery wall, can limit atherosclerosis we constructed HDAd that expresses rabbit interleukin (IL)-10, a potent atheroprotective cytokine, and tested its activity in a rabbit model of early carotid atherogenesis. HDAd expressed immunoreactive, active IL-10 in vitro. In contrast to other HDAd-expressed transgenes, IL-10 expression from HDAd increased significantly between 3 days and 2 weeks after infusion and remained stable for at least 8 weeks. Rising, persistent IL-10 expression was associated with relative persistence of HDAdIL-10 genomes 4 weeks after infusion, compared with HDAdNull genomes. Surprisingly, IL-10 expression had no significant effects on atherosclerotic lesion size, macrophage content, or expression of either adhesion molecules or atherogenic cytokines. These results might be due to inadequate protein expression in vivo or lack of suitability of this rabbit model to reveal IL-10 therapeutic effects. IL-10 remains a promising agent for vascular gene therapy and HDAd remains a promising vector; however, proof of efficacy of HDAdIL-10 is elusive. Future preclinical studies will be aimed at increasing IL-10 expression levels and improving the sensitivity of this animal model to detect atheroprotective effects.
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Affiliation(s)
- Liang Du
- Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195, USA
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Yang H, Chen SC. The effect of interleukin-10 on apoptosis in macrophages stimulated by oxLDL. Eur J Pharmacol 2011; 657:126-30. [PMID: 21296075 DOI: 10.1016/j.ejphar.2011.01.049] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 01/14/2011] [Accepted: 01/25/2011] [Indexed: 11/15/2022]
Abstract
Marked anti-atheromatous effects of the anti-inflammatory cytokine interleukin-10 (IL-10) were observed in several lipid-driven animal models of arteriosclerosis. We have previously demonstrated that IL-10 significantly inhibited lipid uptake in macrophages induced by oxLDL (Wang et al., 2008; Yang et al., 2008b). In this study, we investigated whether IL-10 affects the apoptosis related gene BCL2L11 and BMF expression in macrophages treated with oxLDL from THP-1 cells, which served as macrophage models. Cell apoptosis assays were performed by flow cytometry. Expression of the apoptosis related genes BCL2L11 and BMF mRNA was quantified by real-time RT-PCR (mRNA expression) and Western blotting (protein expression). IL-10 markedly blocked oxLDL induced cells undergoing early stage apoptosis. In the foam cell group, as compared with the macrophage group, the percentage of apoptosis increased by 100%. Here the expression of BCL2L11 was 45% (mRNA) and 41% (protein) elevated, while the expression of BMF was 54% (mRNA) and 44% (protein) elevated. When macrophages were co-stimulated by 100mg/l oxLDL and 20 μg/l IL-10 for 24h, compared with the foam cell group, the percentage of the apoptosis decreased by 21%, the expression of apoptosis related gene BMF was inhibited, the expression of mRNA and protein was both depressed by 23% and 20%, respectively, but the BCL2L11 expression was unchanged. These results may explain why decrement of early stage apoptosis cells was observed during co-stimulation and raise the possibility that IL-10 reduces foam cell undergoing apoptosis partly through down-regulating the expression of BMF, which demonstrates a critical role of IL-10 in anti-atherogenesis.
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Affiliation(s)
- Hong Yang
- Dept. of Biochemistry, Medical College of Tongji University, Shanghai 200092, China.
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Poredos P, Jezovnik MK. In patients with idiopathic venous thrombosis, interleukin-10 is decreased and related to endothelial dysfunction. Heart Vessels 2011; 26:596-602. [PMID: 21267581 DOI: 10.1007/s00380-010-0111-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2010] [Accepted: 12/03/2010] [Indexed: 01/22/2023]
Abstract
The aim of this study was to evaluate the levels of anti-inflammatory interleukin-10 and pro-inflammatory cytokines and their relationship to endothelial function in patients with idiopathic venous thrombosis. Forty-nine eligible patients of both sexes with idiopathic venous thrombosis and 48 matched control subjects were studied. Levels of inflammatory markers were determined. Endothelial function was evaluated by ultrasound measurement of the flow mediated dilatation (FMD) of the brachial artery. Compared to the control group, patients with idiopathic venous thrombosis had significantly lower levels of interleukin-10 1.81 pg/ml (1.53-2.21) versus 2.71 pg/ml (1.84-3.65), p < 0.001. Patients also had increased levels of pro-inflammatory cytokines: interleukin-6 2.37 pg/ml (1.59-4.09) versus 2.03 pg/ml (1.49-2.59), p = 0.025, interleukin-8 3.53 pg/ml (2.94-5.30) versus 2.25 pg/ml (1.77-2.90), p < 0.001. Furthermore, decreased FMD was observed in patients: 5.0% (3.9-6.9) versus 12.7% (10.8-15.6), p < 0.001. FMD was related to levels of interleukin-10 (r = 0.33, p = 0.001) and was inversely related to pro-inflammatory cytokines interleukin-6 (r = -0.34, p = 0.001) and interleukin-8 (r = -0.43, p < 0.001). Patients with idiopathic venous thrombosis have decreased levels of IL-10 and increased levels of pro-inflammatory cytokines. This imbalance indicates that in the stable phase of the disease, patients have an increased systemic inflammatory response. This inflammatory response could be the consequence of the disease, but most probably is involved in the pathogenesis of venous thrombosis.
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Affiliation(s)
- Pavel Poredos
- Department of Vascular Disease, University Medical Centre Ljubljana, Zaloska 7, 1000, Ljubljana, Slovenia.
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Zemse SM, Chiao CW, Hilgers RHP, Webb RC. Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-alpha on the endothelium of murine aorta. Am J Physiol Heart Circ Physiol 2010; 299:H1160-7. [PMID: 20639218 DOI: 10.1152/ajpheart.00763.2009] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
TNF-α is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H(2)O), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37°C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (220 ng·kg(-1)·day(-1)) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001-10 μmol/l) during phenylephrine (10 μmol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses (E(max)) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses (E(max)) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-α by protecting eNOS expression.
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Affiliation(s)
- Saiprasad M Zemse
- Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA.
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Stoica AL, Stoica E, Constantinescu I, Uscatescu V, Ginghina C. Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysfunction, and postoperative prognosis in patients with peripheral arterial disease. J Vasc Surg 2010; 52:103-9. [PMID: 20385468 DOI: 10.1016/j.jvs.2010.01.088] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2009] [Revised: 01/23/2010] [Accepted: 01/28/2010] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the association between interleukin (IL)-6 and IL-10 gene polymorphism and the short-term risk of postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgery and also to evaluate the endothelial function. METHODS AND RESULTS We determined preoperatively IL-6 gene polymorphism (-174 G/C and nt565 G/A), IL-10 polymorphism (-1082G/A, -819C/T, -592C/A), and brachial artery vasodilatation using ultrasound in 48 patients undergoing vascular surgery. Eight patients (16.7%) developed over a period of 30 days cardiovascular events (cardiovascular death, resuscitated cardiac arrest, acute myocardial infarction, unstable angina, stroke). Cardiovascular events were more frequent in the subgroups of patients with genotypes associated with high serum levels of IL-6: -174CC (57.14% vs 12.5% for -174GC genotype and 8% for -174GG, P = .007) and nt565AA (50% vs 17.6% for nt565GA genotype and 8% for nt565GG genotype, P = .021) and in subgroups with haplotypes associated with low serum levels of IL-10: ATA (57.14% vs 14.8% for haplotype ACC and 7.4% for GCC, GCA, GTA, GTC haplotypes, P = .004). Flow-mediated dilatation was significantly lower in patients with IL-6 -174CC genotype (7.05% +/- 1.49% vs 8.41% +/- 1.9% for IL-6 -174GC and 9.42% +/- 2.46% for IL-6 -174GG, P = .009) and IL-6 nt565AA genotype (7.14 +/- 1.61% vs 8.49% +/- 1.91% for IL-6 nt565GA and 9.42% +/- 2.46% for IL-6 nt565GG, P = .018) and in patients with IL-10ATA haplotype (6.45% +/- 0.57% vs 9.13% +/- 2.52% for IL-10ACC and 9.24% +/- 2.09% for IL-10 GCC/GCA/GTA/GTC, P = .004) respectively. CONCLUSIONS IL-6 -174CC and nt565AA genotypes and IL-10ATA haplotypes are correlated with a high short-term risk of acute postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgical revascularization and with endothelial dysfunction in these patients.
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Carvajal CA, Herrada AA, Castillo CR, Contreras FJ, Stehr CB, Mosso LM, Kalergis AM, Fardella CE. Primary aldosteronism can alter peripheral levels of transforming growth factor beta and tumor necrosis factor alpha. J Endocrinol Invest 2009; 32:759-65. [PMID: 19605974 DOI: 10.1007/bf03346533] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
UNLABELLED Primary aldosteronism (PA) is the most common secondary cause of hypertension that has recently been implicated in alterations of the immune system and progression of cardiovascular disease. OBJECTIVE To study the cytokines transforming growth factor beta1 (TGF-beta1), tumor necrosis factor alpha (TNF-alpha), and interleukin 10 (IL-10) in patients with PA and essential hypertensives (EH) and evaluate its association with the renin-angiotensin-aldosterone system. PATIENTS AND METHODS We studied 26 PA and 52 EH patients as controls, adjusted by their blood pressure, body mass index, age, and gender. In both groups, PA and EH, we measured serum aldosterone (SA), plasma renin activity (PRA), and cytokines TGF- beta1, TNF-alpha, and IL-10. In addition, 17 PA patients were treated for 6 months with spironolactone, a mineralocorticoid receptor (MR) antagonist. RESULTS PA patients had lower levels of TGF-beta1 (17.6+/-4.1 vs 34.5+/-20.5 pg/ml, p<0.001) and TNF-alpha (17.0+/-4.4 vs 35.6+/-21.7 pg/ml, p<0.001) and similar IL-10 levels (99.7+/-18.7 vs 89.4+/-49.5 pg/ml, p: ns), as compared with EH controls. TGF-beta1 and TNF-alpha levels showed a remarkable correlation with SA/PRA ratio in the total group (PA+EH). The treatment of PA patients with spironolactone increased the TGF-beta1 levels (18.3+/-5.9 to 28.4+/-6.3 pg/ml, p<0.001), while TNF-alpha, and IL-10 remained unchanged. CONCLUSION Our results showed that PA patients have lower TGF-beta1 and TNF-alpha cytokine serum levels than EH. TGF-beta1 levels were restored with spironolactone, showing a MR-dependent regulation. In this way, the chronic aldosterone excess modifies the TGF-beta1 levels, which could produce an imbalance in the immune system homeostasis that may promote an early proinflammatory cardiovascular phenotype.
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Affiliation(s)
- C A Carvajal
- Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
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Abstract
The vascular endothelium contributes to and is affected by inflammatory processes. Disturbance of the endothelium's morphologic and functional integrity in response to mechanical, immunologic, and chemical injuries reflects the first step in the pathophysiological cascade of atherosclerotic disorders. At the site of an endothelial injury, invading inflammatory cells producing numerous proinflammatory factors promote and amplify both local and systemic inflammation. These early changes on a cellular and subcellular level that precede the clinical manifestation of atherosclerosis are associated with loss of profound physiological functions of the endothelium. One pivotal function of the endothelium is nitric oxide-mediated regulation of vessel tone and blood flow according to the local requirements. The assessment of nitric oxide-mediated endothelial function by different methods revealed a close relation between inflammatory activation and endothelial dysfunction in healthy volunteers, patients at risk, and patients with established cardiovascular disease. Moreover, anti-inflammatory therapeutic interventions do not only have a positive impact on disease progression, but also on endothelial function, thus further providing an indirect line of evidence linking inflammation with endothelial dysfunction.
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Affiliation(s)
- Thomas Trepels
- Department of Internal Medicine III, Division of Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany
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