University of Oulu

Lin, R., Rahtu-Korpela, L., Szabo, Z., Kemppi, A., Skarp, S., Kiviniemi, A. M., Lepojärvi, E. S., Halmetoja, E., Kilpiö, T., Porvari, K., Pakanen, L., Tolva, J., Paakkanen, R., Segersvärd, H., Tikkanen, I., Laine, M., Sinisalo, J., Lakkisto, P., Huikuri, H., … Kerkelä, R. (2022). MiR-185-5p regulates the development of myocardial fibrosis. Journal of Molecular and Cellular Cardiology, 165, 130–140.

MiR‐185‐5p regulates the development of myocardial fibrosis

Saved in:
Author: Lin, Ruizhu1; Rahtu-Korpela, Lea1; Szabo, Zoltan1,2;
Organizations: 1Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Finland
2Division of Cardiology, Research Unit of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland
3Department of Forensic Medicine, Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
4Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland
5Transplantation laboratory, Department of Pathology, University of Helsinki, Finland
6Department of Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Finland
7Unit of Cardiovascular Research, Minerva Institute for Medical Research, Helsinki, Finland
8Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
9Department of Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, Finland
10Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
11Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.8 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2022-08-09


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.

see all

Series: Journal of molecular and cellular cardiology
ISSN: 0022-2828
ISSN-E: 1095-8584
ISSN-L: 0022-2828
Volume: 165
Pages: 130 - 140
DOI: 10.1016/j.yjmcc.2021.12.011
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Academy of Finland [grant number 297094 and 333284 to R.K., grant number 268505 to J.M.]; Finnish Foundation for Cardiovascular Research [to R.L., L.R-K., Z.S., H.H., J.M., J.J. and R.K.]; Sigrid Juselius Foundation, Finland [J.J. and R.K.] and by Jane and Aatos Erkko Foundation [H.H., J.J. and R.K.].
Academy of Finland Grant Number: 297094
Detailed Information: 297094 (Academy of Finland Funding decision)
333284 (Academy of Finland Funding decision)
268505 (Academy of Finland Funding decision)
Copyright information: © 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( nd/4.0/).