title: S100A4 protects the myocardium against ischemic stress.
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.
  
  
  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.
  
  
  CONCLUSIONS
  S100A4 expression protects cardiac myocytes against myocardial ischemia and is required for stabilization of cardiac function after MI.
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA; University Hospital Heidelberg, Internal Medicine III, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Shirin
authors.initials: S
authors.lastname: Doroudgar
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Pearl
authors.initials: P
authors.lastname: Quijada
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA; University Hospital Heidelberg, Internal Medicine III, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Konstandin
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Ilves
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Broughton
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Farid G
authors.initials: FG
authors.lastname: Khalafalla
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Casillas
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Gude
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ornelas
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Thuerauf
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Glembotski
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sussman
authors.affiliation: The San Diego State Heart Institute and Department of Biology, San Diego State University, San Diego, CA 92182, USA; University Hospital Heidelberg, Internal Medicine III, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany. Electronic address: Mirko.voelkers@med.uni-heidelberg.de.
authors.forename: Mirko
authors.initials: M
authors.lastname: Völkers
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D006439:Hemodynamics; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D020257:Ventricular Remodeling
chemical_list: D000071999:S100 Calcium-Binding Protein A4
keywords: Myocardial infarction; Remodeling; S100A4