期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 165, 期 -, 页码 130-140出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2021.12.011
关键词
Myocardial fibrosis; MicroRNAs; Heart failure; Pressure overload
资金
- Academy of Finland [297094, 333284, 268505]
- Finnish Foundation for Cardiovascular Research
- Sigrid Juselius Foundation, Finland
- Jane and Aatos Erkko Foundation
- Academy of Finland (AKA) [333284, 297094, 268505, 297094, 268505, 333284] Funding Source: Academy of Finland (AKA)
In this study, miR-185-5p was identified as a regulator of myocardial fibrosis by targeting the apelin receptor. This finding provides a potential therapeutic target for the treatment of cardiac fibrosis.
Background: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis. Methods and results: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-beta 1 and collagen I. Conclusions: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.
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