MECHANISMS OF COMPLEMENT INDUCED ENDOTHELIAL DYSFUNCTION

补体引起的内皮功能障碍的机制

• 批准号: 2910613
• 负责人: GREGORY L STAHL
• 金额: $ 30.13万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2910613
• 关键词: antibody; complement pathway; coronary artery; disease /disorder model; free radical oxygen; leukocyte activation /transformation; myocardial ischemia /hypoxia; neutrophil; reperfusion; respiratory oxygenation; swine; tissue /cell culture; vascular endothelium

DESCRIPTION: (Adapted from the applicant's abstract) There is considerable recent interest in the activation of complement proteins during the early stages of myocardial ischemia and reperfusion. In the present proposal this research team continue their focus on endothelial injury, with particular emphasis on the alternative complement pathway. They provide excellent evidence that hypoxia alone does not activate this cascade; rather, reperfusion and oxygen radicals produce C5b, the linchpin for sequential assembly of the C5b-9 membrane attack complex. This transmembrane pore complex could directly injure vascular endothelium by a number of mechanisms, including production of oxygen metabolites. The role of the C5a fragments is projected to involve synergistic activation of neutrophils compounding vascular injury. The five year proposal consists of experiments investigating complement mechanisms in isolated vessels (both large and micro-vessels, years 1 and 2), verification of complement deposition after hypoxia-reoxygenation on small and large coronary artery vessels and endothelial cells (year 3), and lastly delineation of the alternative complement pathways during myocardial ischemia-reperfusion in a pig model, with special emphasis on therapeutic attenuation of C5b-9 mediated injury in vivo.

描述：（改编自申请人的摘要）有