Open AccessEndogenous reduction of miR‐185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K
Author(s) -
Li ChuanChang,
Qiu XueTing,
Sun Quan,
Zhou JiPeng,
Yang HuiJun,
Wu WanZhou,
He LingFang,
Tang CanE,
Zhang GuoGang,
Bai YongPing
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14016
Subject(s) - angiogenesis , gene silencing , gene knockdown , microrna , competing endogenous rna , biology , endogeny , angiogenin , in vivo , microbiology and biotechnology , gene expression , reporter gene , cancer research , rna , gene , endocrinology , long non coding rna , biochemistry
Angiogenesis is critical for re‐establishing the blood supply to the surviving myocardium after myocardial infarction ( MI ) in patients with acute coronary syndrome ( ACS ). Micro RNA s are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of micro RNA s in angiogenesis. Eighteen circulating micro RNA s 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 vein endothelial cells ( HUVEC s) 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 HUVEC s, miR‐185‐5p mimics 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 HUVEC s were abolished by CatK gene overexpression, and adenovirus‐mediated CatK gene silencing ablated these enhancive effects in HUVEC s 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 cardiac functions in mice following MI . These actions of miR‐185‐5p agonists were mirrored by in vivo knockdown of CatK in mice with MI . Endogenous reductions of miR‐185‐5p in endothelial cells induced by hypoxia increase CatK gene expression to promote angiogenesis and to accelerate the recovery of cardiac function in mice following MI .