MiR-185-5p regulates the development of myocardial fibrosis. (April 2022)

• Record Type: Journal Article
• Authors: Lin, Ruizhu; Rahtu-Korpela, Lea; Szabo, Zoltan; Kemppi, Anna; Skarp, Sini; Kiviniemi, Antti M.; Lepojärvi, E. Samuli; Halmetoja, Eveliina; Kilpiö, Teemu; Porvari, Katja; Pakanen, Lasse; Tolva, Johanna; Paakkanen, Riitta; Segersvärd, Heli; Tikkanen, Ilkka; Laine, Mika; Sinisalo, Juha; Lakkisto, Päivi; Huikuri, Heikki; Magga, Johanna; Junttila, Juhani; Kerkelä, Risto
• Is Part Of: Journal of molecular and cellular cardiology. Volume 165(2022)
• Page Start: 130
• Page End: 140
• Publication Date: 2022-04
• Subjects: Myocardial fibrosis -- MicroRNAs -- Heart failure -- Pressure overload; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2021.12.011
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: 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-β1 and collagen I. Conclusions: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis. Graphical abstract: Unlabelled Image Highlights: miR-185-5p induces collagen production. Targeting miR-185-5p reduces pressure overload -induced myocardial fibrosis. miR-185-5p targets apelin receptor. miR-185-5p expression is increased in hearts of patients with end-stage heart failure.