Bin Li1, Yu-Hua Liao, Xiang Cheng, Hongxia Ge, Heping Guo, Min Wang. 1. Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract
OBJECTIVE: A number of observations suggest that cytokines may be important modulators in the ventricular remodeling process. It is unclear whether carvedilol modulates myocardial pro-inflammatory and anti-inflammatory cytokines expression. We hypothesized that carvedilol could improve ventricular remodeling partly through the modulation of cytokines. The goal of this study was to evaluate the effects of carvedilol on cardiac cytokines expression as well as on myocardial and extracellular matrix remodeling in rats with acute myocardial infarction. METHODS: Rats with AMI induced by left anterior descending branch ligation were randomized to carvedilol and control group which were further compared to sham-operated group. We studied the effects of 4-weeks therapy with carvedilol starting 24 h after infarction on 1) hemodynamics, 2) tissue weights, 3) myocardial cytokines (TNF-alpha, IL-1beta, IL-6, IL-10 and TGF-beta1) expression by semi-quantitative RT-PCR and immunoblotting, 4) matrix metalloproteinases activity by gelatin zymography, 5) collagen expression by immunohistochemistry, 6) myocardium fetal gene (alpha and beta myosin heavy chain) expression. RESULTS: Treatment with carvedilol 1) reduced the pro-inflammatory cytokines and fibrogenic cytokine TGF-beta1 levels in myocardium and was associated with the amelioration of the elevated left ventricular diastolic pressure. 2) increased anti-inflammatory cytokine, IL-10 protein expression. 3) reduced matrix metalloproteinases-2 and matrix metalloproteinases-9 activity 4) reduced myocardial collagens 5) did not modify fetal gene re-expression. CONCLUSION: Pro-inflammatory, anti-inflammatory and fibrogenic cytokines are all involved in the process of post-infarction myocardial remodeling. One mechanism underlying the beneficial effects of carvedilol on post-infarction myocardial remodeling may be modulation of the balance between pro- and anti-inflammatory cytokines as well as fibrogenic cytokines and extracellular matrix (ECM) remodeling.
OBJECTIVE: A number of observations suggest that cytokines may be important modulators in the ventricular remodeling process. It is unclear whether carvedilol modulates myocardial pro-inflammatory and anti-inflammatory cytokines expression. We hypothesized that carvedilol could improve ventricular remodeling partly through the modulation of cytokines. The goal of this study was to evaluate the effects of carvedilol on cardiac cytokines expression as well as on myocardial and extracellular matrix remodeling in rats with acute myocardial infarction. METHODS:Rats with AMI induced by left anterior descending branch ligation were randomized to carvedilol and control group which were further compared to sham-operated group. We studied the effects of 4-weeks therapy with carvedilol starting 24 h after infarction on 1) hemodynamics, 2) tissue weights, 3) myocardial cytokines (TNF-alpha, IL-1beta, IL-6, IL-10 and TGF-beta1) expression by semi-quantitative RT-PCR and immunoblotting, 4) matrix metalloproteinases activity by gelatin zymography, 5) collagen expression by immunohistochemistry, 6) myocardium fetal gene (alpha and beta myosin heavy chain) expression. RESULTS: Treatment with carvedilol 1) reduced the pro-inflammatory cytokines and fibrogenic cytokine TGF-beta1 levels in myocardium and was associated with the amelioration of the elevated left ventricular diastolic pressure. 2) increased anti-inflammatory cytokine, IL-10 protein expression. 3) reduced matrix metalloproteinases-2 and matrix metalloproteinases-9 activity 4) reduced myocardial collagens 5) did not modify fetal gene re-expression. CONCLUSION: Pro-inflammatory, anti-inflammatory and fibrogenic cytokines are all involved in the process of post-infarction myocardial remodeling. One mechanism underlying the beneficial effects of carvedilol on post-infarction myocardial remodeling may be modulation of the balance between pro- and anti-inflammatory cytokines as well as fibrogenic cytokines and extracellular matrix (ECM) remodeling.
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