title: Increase of fibronectin and osteopontin in porcine hearts following ischemia and reperfusion.
abstract: Following a severe ischemic injury or myocardial infarction, the extracellular matrix (ECM) of the heart is involved in pathophysiological conditions such as dilatation and cardiac dysfunction. Osteopontin (OPN) has been shown to interact with fibronectin suggesting its possible role in matrix organization, stability and wound healing. There is increased expression of OPN in several tissues in response to injury. Therefore, we tested the hypothesis that acute ischemia (2 h), followed by reperfusion (4 h) may induce early OPN and fibronectin in an isolated hemoperfused working porcine heart model. Twenty hearts were prepared and connected to a perfusion system. After 1 h of perfusion, these hearts were randomized to two groups: ten infarcted (MI, ramus circumflexus) and ten non-infarcted hearts (C). In addition, cardiac fibroblasts derived from infarcted, remote and control myocardium were investigated. In both groups, the heart rate, electrolytes, pH, blood gases, and lactate remained similar. The LVEDP and perfusion pressure of MI hearts increased significantly (P<0.05). The total fibronectin and OPN volume contents were clearly elevated in the infarct area. The matrix metalloproteinases (MMP-1 and MMP-8), fibronectin, OPN, TGF-beta1 proteins and the mRNAs for fibronectin, TGF-beta1, and OPN were significantly elevated in the infarct area as compared to the remote area and the non-infarcted hearts. Simultaneously, circulating carboxyterminal propeptide of type I procollagen (PICP) was released in the perfusion medium (threefold versus C). Fibroblast-like cells originating from the infarct area exhibited an enhanced OPN and fibronectin gene and protein expression compared to fibroblasts derived from control myocardium. Our data demonstrate the early appearance of the MMPs (increased collagen degrading enzymes) and PICP (a collagen synthesis marker) following ischemia and reperfusion. Moreover, OPN, fibronectin and TGF-beta1 protein and gene expression are elevated after ischemia and reperfusion in the ex vivo working hemoperfused porcine heart model.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Charité-University Medical School, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Johann
authors.initials: J
authors.lastname: Schönberger
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shakibaei
authors.forename: Shideh
authors.initials: S
authors.lastname: Faramarzi
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Kurth
authors.forename: Britta
authors.initials: B
authors.lastname: Habighorst
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Bauer
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
authors.forename: Gundula
authors.initials: G
authors.lastname: Schulze-Tanzil
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D066298:In Vitro Techniques; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D053495:Osteopontin; D011347:Procollagen / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005353:Fibronectins; D011347:Procollagen; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D020781:Matrix Metalloproteinase 1