Cardioprotective effects of osteopontin-1 during development of murine ischemic cardiomyopathy

Duerr GD, Mesenholl B, Heinemann JC, Zoerlein M, Huebener P, Schneider P, Feisst A, Ghanem A, Tiemann K, Dewald D, Welz A, Dewald O (2014)


Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 2014

Article Number: 124063

DOI: 10.1155/2014/124063

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 (n = 8 /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. © 2014 Georg D. Duerr et al.

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APA:

Duerr, G.D., Mesenholl, B., Heinemann, J.C., Zoerlein, M., Huebener, P., Schneider, P.,... Dewald, O. (2014). Cardioprotective effects of osteopontin-1 during development of murine ischemic cardiomyopathy. BioMed Research International, 2014. https://doi.org/10.1155/2014/124063

MLA:

Duerr, Georg D., et al. "Cardioprotective effects of osteopontin-1 during development of murine ischemic cardiomyopathy." BioMed Research International 2014 (2014).

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