Endogenous reduction of miR ‐185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K

AbstractAngiogenesis is critical for re ‐establishing the blood supply to the surviving myocardium after myocardial infarction (MI) in patients with acute coronary syndrome (ACS). MicroRNAs are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of microRNAs in angiogen esis. Eighteen circulating microRNAs including miR‐185‐5p were differently expressed in plasma from patients with ACS by high‐throughput RNA sequencing. The expressional levels of miR‐185‐5p were dramatically reduced in hearts isolated from mice following MI and cultured human umbilical ve in endothelial cells (HUVECs) under hypoxia, as determined by fluorescence in situ hybridisation and quantitative RT‐PCR. Evidence from computational prediction and luciferase reporter gene activity indicated that cathepsin K (CatK) mRNA is a target of miR‐185‐5p. In HUVECs, miR‐185‐5p mi mics inhibited cell proliferations, migrations and tube formations under hypoxia, while miR‐185‐5p inhibitors performed the opposites. Further, the inhibitory effects of miR‐185‐5p up‐regulation on cellular functions of HUVECs were abolished by CatK gene overexpression, and adenovirus‐me diated CatK gene silencing ablated these enhancive effects in HUVECs under hypoxia. In vivo studies indicated that gain‐function of miR‐185‐5p by agomir infusion down‐regulated CatK gene expression, impaired angiogenesis and delayed the recovery of...

Source: Journal of Cellular and Molecular Medicine - November 18, 2018 Category: Molecular Biology Authors: Chuan ‐Chang Li, Xue‐Ting Qiu, Quan Sun, Ji‐Peng Zhou, Hui‐Jun Yang, Wan‐Zhou Wu, Ling‐Fang He, Can‐E Tang, Guo‐Gang Zhang, Yong‐Ping Bai Tags: ORIGINAL ARTICLE Source Type: research