S100A4 protects the myocardium against ischemic stress

Shirin Doroudgar, Pearl Quijada, Mathias Konstandin, Kelli Ilves, Kathleen Broughton, Farid G. Khalafalla, Alexandria Casillas, Kristine Nguyen, Natalie Gude, Haruhiro Toko, Luis Ornelas, Donna J. Thuerauf, Christopher C. Glembotski, Mark A. Sussman, Mirko Völkers

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background Myocardial infarction is followed by cardiac dysfunction, cellular death, and ventricular remodeling, including tissue fibrosis. S100A4 protein plays multiple roles in cellular survival, and tissue fibrosis, but the relative role of the S100A4 in the myocardium after myocardial infarction is unknown. This study aims to investigate the role of S100A4 in myocardial remodeling and cardiac function following infarct damage. Methods and results S100A4 expression is low in the adult myocardium, but significantly increased following myocardial infarction. Deletion of S100A4 increased cardiac damage after myocardial infarction, whereas cardiac myocyte-specific overexpression of S100A4 protected the infarcted myocardium. Decreased cardiac function in S100A4 Knockout mice was accompanied with increased cardiac remodeling, fibrosis, and diminished capillary density in the remote myocardium. Loss of S100A4 caused increased apoptotic cell death both in vitro and in vivo in part mediated by decreased VEGF expression. Conversely, S100A4 overexpression protected cells against apoptosis in vitro and in vivo. Increased pro-survival AKT-signaling explained reduced apoptosis in S100A4 overexpressing cells. Conclusion S100A4 expression protects cardiac myocytes against myocardial ischemia and is required for stabilization of cardiac function after MI.

Original languageEnglish (US)
Pages (from-to)54-63
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume100
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • Myocardial infarction
  • Remodeling
  • S100A4

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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