RIPC may promotes angiogenesis of myocardium by downregulation of miR-148a

Abstract

Abstract Angiogenesis is essential for repairing of cardiac tissue after myocardial infarction[1]. Remote ischemic preconditioning (RIPC) induced by cycles of transient limb ischemia and reperfusion is a very efficient cardioprotective strategy, which has pleiotropic effects, such as angiogenesis etc[1], [2]. Over the last decades many experimental and clinical studies have proven cardioprotective effects of RIPC, especially in the context of myocardial ischemia/reperfusion (I/R) injury[3]–[5]. However, the detailed mechanisms how RIPC works remains incomplete. Here, we report our investigation about the effects of RIPC in angiogenesis. And a possible mechanism that RIPC promotes angiogenesis by downregulation of miR-148a. In our study, RIPC downregulated miR-148a level in humans’ serum. Moreover, MicroRNA stem loop RT-PCR assays demonstrated that chronic RIPC (cRIPC) had lower expression of miR-148a than one-time RIPC. By analyzing HUVEC cells with overexpression or knockdown of miR-148a, it revealed that knockdown of miR-148a led to overexpression of ROCK1, YAP and Ang2, which also promotes angiogenesis. On the other hand, overexpression of miR-148a inhibited expression of ROCK1, YAP and Ang2. Overexpression of miR-148a also inhibited cell proliferation, migration, and tube formation of HUVEC cells. In conclusion, this study reveals that downregulation of miR-148a may play important role in RIPC by promoting angiogenesis. Downregulation of miR-148a could increase the expression level of ROCK1, YAP and Ang2. ROCK1 and YAP may be involved in the pathway that knockdown or downregulation of miR-148a may enhance angiogenesis through Ang2. The results provide novel understanding of the mechanism of RIPC towards angiogenesis and effect of miR-148a in angiogenesis.