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Increase of fibronectin and osteopontin in porcine hearts following ischemia and reperfusion

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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-β1 proteins and the mRNAs for fibronectin, TGF-β1, 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-β1 protein and gene expression are elevated after ischemia and reperfusion in the ex vivo working hemoperfused porcine heart model.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Charité-University Medical School, Garystr. 5, 14195, Berlin, Germany

    Peter Kossmehl, Shideh Faramarzi, Ekkehard Kurth, Britta Habighorst, Rüdiger von Bauer, Markus Wehland, Reinhold Kreutz, Martin Paul & Daniela Grimm

  2. Department of Nuclear Medicine, University of Regensburg, Regensburg, Germany

    Johann Schönberger

  3. Institute of Anatomy, Benjamin Franklin Campus, Charité-University Medicine Berlin, Berlin, Germany

    Gundula Schulze-Tanzil

  4. Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany

    Mehdi Shakibaei

  5. Department of Trauma and Reconstructive Surgery, Benjamin Franklin Campus, Charité-University Medicine Berlin, Berlin, Germany

    Manfred Infanger

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  1. Peter Kossmehl
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  2. Johann Schönberger
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  11. Gundula Schulze-Tanzil
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  12. Martin Paul
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  13. Daniela Grimm
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Corresponding author

Correspondence to Daniela Grimm.

Additional information

This research was supported by the Deutsche Forschungsgemeinschaft (DFG) grants GR 1039/7-1 and GR 1039/7-2 to D.G.

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Kossmehl, P., Schönberger, J., Shakibaei, M. et al. Increase of fibronectin and osteopontin in porcine hearts following ischemia and reperfusion. J Mol Med 83, 626–637 (2005). https://doi.org/10.1007/s00109-005-0642-8

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  • DOI: https://doi.org/10.1007/s00109-005-0642-8

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