Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Peripheral Vascular Disease, Cardiovascular System & Cardiology, ACE gene polymorphism, cardiac fibrosis, isoproterenol, pro-fibrotic factors, pro-inflammatory factors, RENIN-ANGIOTENSIN, MYOCARDIAL HYPERTROPHY, ALDOSTERONE SYSTEM, II RECEPTORS, FIBROBLASTS, HEART, IDENTIFICATION, INFLAMMATION, STIMULATION, INHIBITION, Animals, Cardiomegaly, Cell Proliferation, Chemokine CCL2, Collagen, Endothelin-1, Fibroblasts, Fibronectins, Fibrosis, Gene Expression Regulation, Heart Ventricles, Inflammation Mediators, Isoproterenol, Matrix Metalloproteinase 2, Myocardium, Peptidyl-Dipeptidase A, Polymorphism, Single Nucleotide, RNA, Messenger, Rats, Transforming Growth Factor beta1, 0606 Physiology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology

Abstract:

INTRODUCTION: Isoproterenol treatment of Brown Norway and Lewis rats (high and low plasma angiotensin-I-converting enzyme activity, respectively) results in similar cardiac hypertrophy but higher cardiac fibrosis in Brown Norway rats. MATERIALS AND METHODS: Rats were infused in vivo with isoproterenol for two or 10 days. Cardiac fibrosis and inflammation were evaluated histochemically. We measured the mRNAs of pro-fibrotic factors (transforming growth factor beta(1), endothelin-1) and pro-inflammatory factors (monocyte chemoattractant protein-1). In studies with cardiac fibroblasts incubated with isoproterenol in vitro , we measured cell proliferation, angiotensin-I-converting enzyme and matrix metalloprotease 2 activities and deposition of collagen type I and fibronectin. RESULTS: After treatment with isoproterenol for two days, there were large areas of myocardial injury and numerous inflammatory foci in the left ventricle, these being greater in Brown-Norway than in Lewis rats. After treatment with isoproterenol for 10 days, there were large areas of damage with extensive collagen deposition only in the left ventricle; both strains exhibited this damage which was, however, more severe in Brown-Norway than in Lewis rats. After treatment with isoproterenol for two, but not 10, days, greater amounts of monocyte chemoattractant protein-1 mRNA were found in Brown Norway than in Lewis rats. Cell proliferation, activities of angiotensin-I-converting enzyme and matrix metalloprotease 2, amounts of collagen type I and fibronectin were similar in cardiac fibroblasts from both strains; changes after isoproterenol (10 microM) were also similar in both strains. CONCLUSION: We conclude that the greater cardiac fibrosis in Brown Norway rats treated with isoproterenol correlates with the early and higher expression of proinflammatory factors.