Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury
Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury
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DOI：
10.1016/j.molimm.2009.08.017
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发表时间：
2009-12-01
影响因子：
3.6
通讯作者：
Stahl, Gregory L.
中科院分区：
文献类型：
--
作者：
Gorsuch, W. Brian;Guikema, Benjamin J.;Stahl, Gregory L.
眼镜蛇蛇毒因子(CVF)是眼镜蛇蛇毒中的一种补体激活蛋白，其功能类似于Ob，几十年来一直被用来分解血清，以研究补体在许多疾病模型系统中的作用。由于免疫原性问题，将CVF用于临床被认为是不切实际的。最近，CVF的人源化被证明产生了一种有效的CVF样分子。在这项研究中，我们证明了重组人源化CVF(HC3-1496)处理的小鼠可以保护心肌免受缺血/再灌注(MI/R)损伤，从而保护心功能。此外，使用HC3-1496治疗后，未观察到MI/R后心肌中的C3沉积。HC3-1496导致补体激活和C3耗尽，但保留了C5滴度。这些数据表明，与CVF不同，HC3-1496在小鼠体内不形成C5转换酶，类似于最近在人类血清/血浆中的研究。这些结果表明人源化CVF(HC3-496)对补体激活所致的缺血心肌再灌注损伤具有保护作用，是一种潜在的临床应用的新的抗补体疗法。(C)2009爱思唯尔有限公司。保留所有权利。
Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles Ob, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use. (C) 2009 Elsevier Ltd. All rights reserved.