MicroRNA-101 Inhibited Postinfarct Cardiac Fibrosis and Improved Left Ventricular Compliance via the FBJ Osteosarcoma Oncogene/Transforming Growth Factor-β1 Pathway

被引：317

作者：

Pan, Zhenwei ^{[1
]}

Sun, Xuelin ^{[1
]}

Shan, Hongli ^{[1
]}

Wang, Ning ^{[1
]}

Wang, Jinghao ^{[1
]}

Ren, Jinshuai ^{[1
]}

Feng, Shuya ^{[1
]}

Xie, Liangjun ^{[1
]}

Lu, Chunying ^{[1
]}

Yuan, Ye ^{[1
]}

Zhang, Yang ^{[1
]}

Wang, Ying ^{[1
]}

Lu, Yanjie ^{[1
]}

Yang, Baofeng ^{[1
]}

机构：

[1] Harbin Med Univ, Dept Pharmacol, Minist Educ, Key Lab Cardiovasc Res,State Prov Key Labs Biomed, Harbin 150081, Heilongjiang, Peoples R China

来源：

CIRCULATION | 2012年 / 126卷 / 07期

基金：

中国国家自然科学基金;

关键词：

fibrosis; heart failure; microRNAs; MYOCARDIAL-INFARCTION; EXPRESSION; HEART; HYPERTROPHY; CONTRIBUTES; FIBROBLAST; ACTIVATION; PATTERN; MIR-133;

D O I：

10.1161/CIRCULATIONAHA.112.094524

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Cardiac interstitial fibrosis is a major cause of the deteriorated performance of the heart in patients with chronic myocardial infarction. MicroRNAs (miRs) have recently been proven to be a novel class of regulators of cardiovascular diseases, including those associated with cardiac fibrosis. This study aimed to explore the role of miR-101 in cardiac fibrosis and the underlying mechanisms. Methods and Results-Four weeks after coronary artery ligation of rats, the expression of miR-101a and miR-101b (miR-101a/b) in the peri-infarct area was decreased. Treatment of cultured rat neonatal cardiac fibroblasts with angiotensin II also suppressed the expression of miR-101a/b. Forced expression of miR-101a/b suppressed the proliferation and collagen production in rat neonatal cardiac fibroblasts, as revealed by cell counting, MTT assay, and quantitative reverse transcription-polymerase chain reaction. The effect was abrogated by cotransfection with AMO-101a/b, the antisense inhibitors of miR-101a/b. c-Fos was found to be a target of miR-101a because overexpression of miR-101a decreased the protein and mRNA levels of c-Fos and its downstream protein transforming growth factor-beta 1. Silencing c-Fos by siRNA mimicked the antifibrotic action of miR-101a, whereas forced expression of c-Fos protein canceled the effect of miR-101a in cultured cardiac fibroblasts. Strikingly, echocardiography and hemodynamic measurements indicated remarkable improvement of the cardiac performance 4 weeks after adenovirus-mediated overexpression of miR-101a in rats with chronic myocardial infarction. Furthermore, the interstitial fibrosis was alleviated and the expression of c-Fos and transforming growth factor-beta 1 was inhibited. Conclusion-Overexpression of miR-101a can mitigate interstitial fibrosis and the deterioration of cardiac performance in postinfarct rats, indicating the therapeutic potential of miR-101a for cardiac disease associated with fibrosis. (Circulation. 2012;126:840-850.)

引用

页码：840 / +

页数：29

共 38 条

[1] Effects of amiodarone on electrical and structural remodeling induced in a canine rapid pacing-induced persistent atrial fibrillation model [J].