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BioMed Research International
Volume 2014, Article ID 124063, 15 pages
http://dx.doi.org/10.1155/2014/124063
Research Article

Cardioprotective Effects of Osteopontin-1 during Development of Murine Ischemic Cardiomyopathy

1Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
2Department of Pediatric Cardiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
3Department of Medicine I, University Clinical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg, Germany
4Department of Radiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
5Department of Medicine II and Cardiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
6Isar Heart Center, Isar Kliniken, Sonnenstraße 24-26, 80331 Munich, Germany
7Department of Anesthesiology and Intensive Care, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany

Received 27 January 2014; Revised 21 April 2014; Accepted 23 April 2014; Published 29 May 2014

Academic Editor: Dario Coletti

Copyright © 2014 Georg D. Duerr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Repetitive brief ischemia and reperfusion (I/R) is associated with ventricular dysfunction in pathogenesis of murine ischemic cardiomyopathy and human hibernating myocardium. We investigated the role of matricellular protein osteopontin-1 (OPN) in murine model of repetitive I/R. One 15-min LAD-occlusion followed by reperfusion was performed daily over 3, 5, and 7 consecutive days in C57/Bl6 wildtype- (WT-) and OPN−/−-mice (/group). After echocardiography hearts were processed for histological and mRNA-studies. Cardiac fibroblasts were isolated, cultured, and stimulated with TGF-β1. WT-mice showed an early, strong, and cardiomyocyte-specific osteopontin-expression leading to interstitial macrophage infiltration and consecutive fibrosis after 7 days I/R in absence of myocardial infarction. In contrast, OPN−/−-mice showed small, nontransmural infarctions after 3 days I/R associated with significantly worse ventricular dysfunction. OPN−/−-mice had different expression of myocardial contractile elements and antioxidative mediators and a lower expression of chemokines during I/R. OPN−/−-mice showed predominant collagen deposition in macrophage-rich small infarctions. We found lower induction of tenascin-C, MMP-9, MMP-12, and TIMP-1, whereas MMP-13-expression was higher in OPN−/−-mice. Cultured OPN−/−-myofibroblasts confirmed these findings. In conclusion, osteopontin seems to modulate expression of contractile elements, antioxidative mediators, and inflammatory response and subsequently remodel in order to protect cardiomyocytes in murine ischemic cardiomyopathy.