Cardioprotective Effects of Osteopontin-1 during Development of Murine Ischemic Cardiomyopathy
| Autor: | Georg D. Duerr, Daniela Dewald, Martin Zoerlein, Andreas Feisst, Alexander Ghanem, Jan C. Heinemann, Peter Huebener, Armin Welz, Oliver Dewald, Prisca Schneider, Bettina Mesenholl, Klaus Tiemann |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Article Subject Myocardial Infarction Myocardial Ischemia Ischemia lcsh:Medicine Myocardial Reperfusion Injury General Biochemistry Genetics and Molecular Biology Pathogenesis Mice stomatognathic system Fibrosis medicine Animals Humans Myocytes Cardiac Myocardial infarction Osteopontin Hibernating myocardium Ischemic cardiomyopathy General Immunology and Microbiology biology business.industry lcsh:R Matricellular protein Tenascin General Medicine Fibroblasts medicine.disease Matrix Metalloproteinases Mice Inbred C57BL Disease Models Animal biology.protein Collagen medicine.symptom Cardiomyopathies business Research Article |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2014 (2014) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2014/124063 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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