Nature Medicine11, 298 - 304 (2005)
Published online: 20 February 2005; Corrected online: 23 February 2005 | doi:10.1038/nm1198
The fibrin-derived peptide B15−42 protects the myocardium against ischemia-reperfusion injury
Peter Petzelbauer1, 2, Paula A Zacharowski3, Yasuhiro Miyazaki1, Peter Friedl1, Georg Wickenhauser1, Francis J Castellino4, Marion Gröger2, Klaus Wolff1, 2
& Kai Zacharowski3
1
Department of General Dermatology, Medical University of Vienna, 18-20 Waehringer Guertel, Vienna, 1090, Austria.
2
Ludwig Boltzmann Institute for Angiogenesis, Microcirculation and Inflammation, Medical University of Vienna, 18-20 Waehringer Guertel, Vienna, 1090, Austria.
3
Molecular Cardioprotection & Inflammation Group, Department of Anesthesia, University Hospital of Dusseldorf, Moorenstr 5, Dusseldorf, 40225, Germany.
4
W.M. Keck Center for Transgene Research, 434 Stepan Hall of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
In the event of a myocardial infarction, current interventions aim to reopen the occluded vessel to reduce myocardial damage and injury. Although reperfusion is essential for tissue salvage, it can cause further damage and the onset of inflammation. We show a novel anti-inflammatory effect of a fibrin-derived peptide, B15−42. This peptide competes with the fibrin fragment N-terminal disulfide knot-II (an analog of the fibrin E1 fragment) for binding to vascular endothelial (VE)-cadherin, thereby preventing transmigration of leukocytes across endothelial cell monolayers. In acute or chronic rat models of myocardial ischemia-reperfusion injury, B15−42 substantially reduces leukocyte infiltration, infarct size and subsequent scar formation. The pathogenic role of fibrinogen products is further confirmed in fibrinogen knockout mice, in which infarct size was substantially smaller than in wild-type animals. Our findings conclude that the interplay of fibrin fragments, leukocytes and VE-cadherin contribute to the pathogenesis of myocardial damage and reperfusion injury. The naturally occurring peptide B15−42 represents a potential candidate for reperfusion therapy in humans.
NOTE: In the HTML version of this paper originally published online, the name of an author was given incorrectly. The correct name for Peter Fried is Peter Friedl. Also, the first affiliation was given incorrectly. The correct affiliation is Department of General Dermatology, Medical University of Vienna, 18-20 Waehringer Guertel, Vienna, 1090, Austria. These errors have been corrected in the HTML version of the article.
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15−42 protects the myocardium against ischemia-reperfusion injury
15−42. This peptide competes with the fibrin fragment N-terminal disulfide knot-II (an analog of the fibrin E1 fragment) for binding to vascular endothelial (VE)-cadherin, thereby preventing transmigration of leukocytes across endothelial cell monolayers. In acute or chronic rat models of myocardial ischemia-reperfusion injury, B
