MiR-135b-5p and MiR-499a-3p Promote Cell Proliferation and Migration in Atherosclerosis by Directly Targeting MEF2C

作者

Xu, ZL;Han, YM;Liu, JY;Jiang, F;Hu, HL;Wang, Y;Liu, QJ;Gong, YQ;Li, X

作者单位

[Xu, Zhiliang; Hu, Huili; Wang, Yan; Liu, Qiji; Gong, Yaoqin; Li, Xi] Shandong Univ, Sch Med, Key Lab Expt Teratol, Inst Med Genet,Minist Educ, Jinan 250012, Shandong, Peoples R China.;-;[Han, Yeming] Shandong Univ, Qilu Hosp, Dept Cardiol, Jinan 250012, Shandong, Peoples R China.;-;[Liu, Jiying] Shandong Univ, Shandong Prov Hosp, Dept Intervent Treatment, Jinan 250021, Shandong, Peoples R China.;-;[Jiang, Fan] Shandong Univ, Qilu Hosp, Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China.;-;[Jiang, Fan] Shandong Univ, Qilu Hosp, Minist Hlth, Jinan 250012, Shandong, Peoples R China.

摘要

Proliferation and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are critical processes involved in atherosclerosis. Recent studies have revealed that microRNAs (miRNAs) can be detected in circulating blood with a stable form and the expression profiles differ in many cellular processes associated with coronary artery disease (CAD). However, little is known about their role, especially serum-derived miRNAs, in ECs and VSMCs phenotype modulation during atherosclerosis. We compared the miRNA expressions in serum samples from 13 atherosclerotic CAD patients and 5 healthy control subjects and identified 36 differentially expressed miRNAs. The expression of selected miRNAs (miR-135b-5p and miR-499a-3p) was further validated in 137 serum samples. Interestingly, miR-135b-5p and miR-499a-3p directly regulated a common target gene: myocyte enhancer factor 2C (MEF2C) which plays an important role in modulating cell phenotype of cardiovascular systems. Furthermore, our results indicated that the 2 elevated miRNAs could jointly promote ECs and VSMCs proliferation and migration by repressing MEF2C expression. Together, our findings demonstrated a serum-based miRNA expression profile for atherosclerotic CAD patients, potentially revealing a previously undocumented mechanism for cell proliferation and migration mediated by miR-135b-5p and miR-499a-3p, and might provide novel insights into the role of circulating miRNAs in atherosclerosis pathogenesis.

关键词

CORONARY-ARTERY-DISEASE; CIRCULATING MICRORNAS; ENDOTHELIAL-CELLS; EXPRESSION; INFLAMMATION; REGULATOR; DIFFERENTIATION; MICROPARTICLES; ANGIOGENESIS; STATINS

基本信息

所属机构:

归属医师: 刘继英

PMID：26184978

UT：000358040200001

刊名:SCIENTIFIC REPORTS

年，卷(期):2015年5卷

DOI：10.1038/srep12276

附件：

收录: SCIE