Endogenous reduction of miR-185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K
| Autor: | Chuan-Chang Li, Hui-Jun Yang, Xue-Ting Qiu, Ji-Peng Zhou, Yong-Ping Bai, Guogang Zhang, Ling-Fang He, Wan-Zhou Wu, Can-E Tang, Quan Sun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Angiogenesis Cathepsin K Myocardial Infarction Down-Regulation Gene Expression Umbilical vein Cell Line acute coronary syndrome Mice angiogenesis 03 medical and health sciences 0302 clinical medicine microRNA Gene expression Human Umbilical Vein Endothelial Cells medicine Animals Humans Gene silencing Myocytes Cardiac RNA Messenger Hypoxia MiR‐185 Cell Proliferation Gene knockdown Chemistry Myocardium Endothelial Cells Recovery of Function Original Articles Cell Biology Hypoxia (medical) Up-Regulation MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article medicine.symptom |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| DOI: | 10.1111/jcmm.14016 |
| Popis: | Angiogenesis 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 angiogenesis. 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 vein 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 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 HUVECs were abolished by CatK gene overexpression, and adenovirus‐mediated 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 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. |
| Databáze: | OpenAIRE |
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