摘要
Background: Excessive proliferation of cardiac fibroblasts plays a critical role in myocardial remodeling and the development of chronic heart failure, and the inhibition of cardiac fibroblast proliferation may help in the prevention of heart failure. Recent studies indicate that aldosterone promotes fibroblast proliferation and that ERK1/2 is critically involved in this process. However, whether aldosterone promotes p-ERK1/2 expression in cardiac fibroblasts via the classic genomic or rapid nongenomic pathway is not fully understood, and the effect of statins on both of these pathways is poorly studied. In this study, we investigated the role of the ERK1/2 pathway in the antiproliferative effects of atorvastatin, in the context of aldosterone-induced cardiac fibroblast proliferation. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5-bromo-20-deoxyuridine assays and flow cytometry analysis were used to examine the inhibitory effects of atorvastatin on aldosterone- induced cardiac fibroblast proliferation and cell cycle progression. Confocal microscopy in conjunction with immunofluorescence and Western blot analysis were used to detect protein expression level. Results: Atorvastatin effectively inhibited aldosterone-induced cardiac fibroblast proliferation and blocked cell cycle progression by arresting the cells at the G(0)/G(1) phase. Aldosterone-induced cyclin D1 and cyclin E2 expression was markedly suppressed by atorvastatin. In addition, atorvastatin significantly blocked the aldosterone-induced p-ERK1/2 expression in the genomic pathway but had no effect on the nongenomic pathway of the aldosterone-induced p-ERK1/2 expression. Conclusions: ERK1/2 is essential for cardiac fibroblast proliferation induced by aldosterone. Atorvastatin effectively suppressed aldosterone-induced cardiac fibroblast proliferation and cell cycle progression, which were associated with the inhibition of the p-ERK1/2 expression in the genomic pathway and subsequent cyclin D1 and cyclin E2 expression.
- 出版日期2013-6
- 单位河北医科大学