Functional Screening Identifies MicroRNAs as Multi-Cellular Regulators of Heart Failure

Robin Verjans, Wouter J. A. Derks, Kerstin Korn, Birte Soennichsen, Rick E. W. van Leeuwen, Blanche Schroen, Marc van Bilsen, Stephane Heymans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Web of Science)

Abstract

Heart failure (HF) is the leading cause of death in the Western world. Pathophysiological processes underlying HF development, including cardiac hypertrophy, fibrosis and inflammation, are controlled by specific microRNAs (miRNAs). Whereas most studies investigate miRNA function in one particular cardiac cell type, their multicellular function is poorly investigated. The present study probed 194 miRNAs-differentially expressed in cardiac inflammatory disease - for regulating cardiomyocyte size, cardiac fibroblasts collagen content, and macrophage polarization. Of the tested miRNAs, 13%, 26%, and 41% modulated cardiomyocyte size, fibroblast collagen production, and macrophage polarization, respectively. Seventeen miRNAs affected all three cellular processes, including miRNAs with established (miR-210) and unknown roles in cardiac pathophysiology (miR-145-3p). These miRNAs with a multi-cellular function commonly target various genes. In-depth analysis in vitro of previously unstudied miRNAs revealed that the observed phenotypical alterations concurred with changes in transcript and protein levels of hypertrophy-, fibrosis- and inflammation-related genes. MiR-145-3p and miR-891a-3p were identified to regulate the fibrotic response, whereas miR-223-3p, miR-486-3p, and miR-488-5p modulated macrophage activation and polarisation. In conclusion, miRNAs are multicellular regulators of different cellular processes underlying cardiac disease. We identified previously undescribed roles of miRNAs in hypertrophy, fibrosis, and inflammation, and attribute new cellular effects to various well-known miRNAs.

Original languageEnglish
Article number6055
Number of pages15
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 15 Apr 2019

Keywords

  • EXPRESSION PROFILES
  • CARDIAC-HYPERTROPHY
  • THERAPEUTIC TARGET
  • MACROPHAGES
  • FIBROSIS
  • FAMILY
  • POLARIZATION
  • DYSFUNCTION
  • ACTIVATION
  • APOPTOSIS

Cite this