title: Cardioprotective effects of osteopontin-1 during development of murine ischemic cardiomyopathy.
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- β 1. 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.
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Georg D
authors: GD
authors: Duerr
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany ; Department of Pediatric Cardiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Bettina
authors: B
authors: Mesenholl
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Jan C
authors: JC
authors: Heinemann
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Martin
authors: M
authors: Zoerlein
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany ; Department of Medicine I, University Clinical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg, Germany.
authors: Peter
authors: 0000-0001-7558-7625
authors: P
authors: Huebener
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Prisca
authors: 0000-0001-5871-9307
authors: P
authors: Schneider
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany ; Department of Radiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Andreas
authors: 0000-0002-5672-3297
authors: A
authors: Feisst
authors: Department of Medicine II and Cardiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Alexander
authors: A
authors: Ghanem
authors: Department of Medicine II and Cardiology, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany ; Isar Heart Center, Isar Kliniken, Sonnenstraße 24-26, 80331 Munich, Germany.
authors: Klaus
authors: K
authors: Tiemann
authors: Department of Anesthesiology and Intensive Care, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Daniela
authors: 0000-0002-7489-804X
authors: D
authors: Dewald
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Armin
authors: A
authors: Welz
authors: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.
authors: Oliver
authors: 0000-0001-5216-7978
authors: O
authors: Dewald
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000503:physiopathology; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism*
chemical_list: C506896:Spp1 protein, mouse; D019063:Tenascin; D053495:Osteopontin; D003094:Collagen; D020782:Matrix Metalloproteinases