Terminal complement components in myocardial ischemia

心肌缺血中的终末补体成分

• 批准号: 6793430
• 负责人: DEEPAK L BHOLE
• 金额: $ 2.3万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2004-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793430
• 关键词: SDS polyacrylamide gel electrophoresis; affinity chromatography; cardiac myocytes; complement pathway regulation; enzyme linked immunosorbent assay; epitope mapping; gene expression; genetic regulation; heart function; immunocytochemistry; immunofluorescence technique; laboratory rat; liquid chromatography mass spectrometry; microarray technology; myocardial ischemia /hypoxia; pathologic process; polymerase chain reaction; postdoctoral investigator; reperfusion

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.

描述（由申请人提供）：补体在心肌缺血/再灌注（MI/R）损伤的发病机制中起着关键作用。大量研究表明，使用抑制补体系统的疗法可显着降低 MI/R 损伤的程度。该实验室的结果表明，在 C5 水平抑制补体系统可显着减轻 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 中发挥着极其重要的作用。该研究项目将通过利用多方面的方法研究 C5b-9 和 C5a 的贡献，描述 C5a 和 C5b-9 在 MI/R 损伤过程中的作用。此外，将通过使用微阵列分析鉴定受C5a和/或C5b-9调节的基因来表征涉及C5a和C5b-9有害作用的分子机制。根据该项目获得的结果，开发可提供针对 MI/R 损伤保护的治疗分子具有强大的潜力。