MicroRNA‑93 promotes angiogenesis and attenuates remodeling via inactivation of the Hippo/Yap pathway by targeting Lats2 after myocardial infarctionω.

Abstract

Inactivation of the Hippo pathway protects the myocardium from cardiac ischemic injury. MicroRNAs (miRs) have been reported to play pivotal roles in the progression of myocardial infarction (MI). The present study examined whether miR-93 could promote angiogenesis and attenuate remodeling after MI via inactivation of the Hippo/Yes-associated protein (Yap) pathway, by targeting large tumor suppressor kinase 2 (Lats2). It was identified that transfection of human umbilical vein endothelial cells with miR-93 mimic significantly decreased Lats2 expression and Yap phosphorylation, increased cell viability and migration, and attenuated cell apoptosis following hypoxia/reoxygenation injury. Moreover, increased expression of miR-93 resulted in an improvement of cardiac function, promotion of angiogenesis and attenuation of remodeling after MI. Additionally, miR-93 overexpression significantly decreased intracellular adhesion molecule 1 and vascular cell adhesion protein 1 expression levels, as well as attenuated the infiltration of neutrophils and macrophages into the myocardium after MI. Furthermore, it was found that miR-93 overexpression significantly suppressed Lats2 expression and decreased the levels of phosphorylated Yap in the myocardium after MI. Collectively, the present results suggested that miR-93 may exert a protective effect against MI via inactivation of the Hippo/Yap pathway by targeting Lats2.