Abstract

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, B_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_15–42 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 B_15–42 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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