Terminal complement components in myocardial ischemia

描述（申请人提供）：补体在心肌缺血/再灌注（MI/R）损伤的发病机制中起关键作用。许多研究表明，使用抑制补体系统的疗法可以显著降低心肌梗死/心肌梗死损伤的程度。本实验室的结果表明，补体系统在C5水平上的抑制可显著减轻MI/R损伤。然而，C5a与C5b-9复合物在MI/R损伤中的确切作用尚不清楚。此外，C5a与C5b-9形成的下游调控途径尚未阐明。我们假设C5b-9（膜攻击复合体）在MI/R中起着极其重要的作用。本研究项目将利用多方面的方法来研究C5b-9和C5b-9在心肌梗死/再灌注损伤中的作用。此外，C5a和C5b-9有害作用的分子机制将通过使用微阵列分析鉴定受C5a和/或C5b-9调控的基因来表征。基于该项目获得的结果，开发治疗性分子以保护心肌/R损伤具有很大的潜力。

DESCRIPTION (provided by applicant): Complement plays a pivotal role in the pathogenesis of myocardial ischemia/reperfusion (MI/R) injury. Numerous studies have demonstrated significant reduction in the degree of MI/R injury using therapies, which inhibit the complement system. Results from this lab show that inhibition of the complement system at the level of C5 significantly attenuates MI/R injury. However, the exact role of C5a versus C5b-9 complex in MI/R injury is unknown. In addition, the regulatory pathways downstream of C5a versus C5b-9 formation have not been elucidated. We hypothesize that C5b-9 (membrane attack complex) plays an extremely important role in MI/R. This research project will delineate the role of C5a and C5b-9 during MI/R injury by utilizing a multi faceted approach for investigating the contribution of C5b-9 and C5a. Furthermore, the molecular mechanisms involved in the deleterious effects of C5a and C5b-9 will be characterized by identifying genes, which are regulated by C5a and/or C5b-9, using microarray analysis. There is a strong potential for development of therapeutic molecules which provide protection from MI/R injury, based on the 'results obtained from this project.