The fibrin-derived peptide Bβ15-42 protects the myocardium against ischemia-reperfusion injury
The fibrin-derived peptide Bβ15-42 protects the myocardium against ischemia-reperfusion injury
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DOI：
10.1038/nm1198
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发表时间：
2005-03-01
期刊：
影响因子：
82.9
通讯作者：
Zacharowski, K
中科院分区：
文献类型：
--
作者：
Petzelbauer, P;Zacharowski, PA;Zacharowski, K
在心肌梗死的情况下，目前的干预措施旨在重新开放闭塞的血管，以减少心肌损伤和损伤。虽然再灌注对于挽救组织是必不可少的，但它可能会导致进一步的损伤和炎症的发生。我们展示了一种新的纤维蛋白衍生多肽Bβ(15-42)的抗炎作用。这种多肽与纤维蛋白片段N-末端二硫键结-II(纤维蛋白E1片段的类似物)竞争结合血管内皮细胞(VE)-钙粘蛋白，从而阻止白细胞跨内皮细胞单层迁移。在急性或慢性心肌缺血-再灌注损伤的大鼠模型中，Bβ(15-42)显著减少白细胞的渗透、梗死面积和随后的瘢痕形成。纤维蛋白原产品的致病作用在纤维蛋白原基因敲除小鼠中得到进一步证实，在这些小鼠中，梗塞面积大大小于野生型动物。我们的研究结果表明，纤维蛋白片段、白细胞和VE-钙粘附素的相互作用参与了心肌损伤和再灌注损伤的发病机制。自然产生的Bβ多肽(15-42)代表了人类再灌注治疗的潜在候选者。
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 beta(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 beta(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 beta(15-42) represents a potential candidate for reperfusion therapy in humans.