MicroRNA-532 protects the heart in acute myocardial infarction, and represses prss23, a positive regulator of endothelial-to-mesenchymal transition

Ahmed S. Bayoumi, Jian Peng Teoh, Tatsuya Aonuma, Zhize Yuan, Xiaofen Ruan, Yaoliang Tang, Huabo Su, Neal L. Weintraub, Il Man Kim

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Aims Acute myocardial infarction (MI) leads to cardiac remodelling and development of heart failure. Insufficient myocardial capillary density after MI is considered a critical determinant of this process. MicroRNAs (miRs), negative regulators of gene expression, have emerged as important players in MI. We previously showed that miR-532-5p (miR-532) is upregulated by the β-arrestin-biased β-adrenergic receptor antagonist (β-blocker) carvedilol, which activates protective pathways in the heart independent of G protein-mediated second messenger signalling. Here, we hypothesize that β2-adrenergic receptor/β-arrestin-responsive miR-532 confers cardioprotection against MI. Methods and results Using cultured cardiac endothelial cell (CEC) and in vivo approaches, we show that CECs lacking miR-532 exhibit increased transition to a fibroblast-like phenotype via endothelial-to-mesenchymal transition (EndMT), while CECs over-expressing miR-532 display decreased EndMT. We also demonstrate that knockdown of miR-532 in mice causes abnormalities in cardiac structure and function as well as reduces CEC proliferation and cardiac vascularization after MI. Mechanistically, cardioprotection elicited by miR-532 is in part attributed to direct repression of a positive regulator of maladaptive EndMT, prss23 (a protease serine 23) in CECs. Conclusions In conclusion, these findings reveal a pivotal role for miR-532-prss23 axis in regulating CEC function after MI, and this novel axis could be suitable for therapeutic intervention in ischemic heart disease.

Original languageEnglish (US)
Pages (from-to)1603-1614
Number of pages12
JournalCardiovascular research
Volume113
Issue number13
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Keywords

  • Biased G protein-coupled receptor signalling
  • Cardioprotection
  • Endothelial-to-mesenchymal transition
  • MicroRNAs
  • β-Arrestin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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