MATRIX METALLOPROTEINASES ON ENDOTHELIAL FUNCTION IN ATHEROSCLEROSIS

基质金属蛋白酶对动脉粥样硬化内皮功能的影响

• 批准号: 7377026
• 负责人: WILLIAM G HAYNES
• 金额: $ 2.45万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377026
• 关键词: MATRIX; METALLOPROTEINASES; ENDOTHELIAL; FUNCTION; ATHEROSCLEROSIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Matrix metalloproteinase-9 (MMP-9) has been found to be enzymatically active in atherosclerotic plaques. It was found in 83% of specimens obtained from the "culprit" coronary lesions of patients with unstable angina. Elevated levels of MMP-9 have also been reported in patients with acute coronary syndromes. These findings raise the possibility that inhibitors of MMP-9 might provide a novel form of therapy for stabilization of the atherosclerotic lesions of patients with coronary artery disease and prevention of acute ischemic syndromes. Doxycycline (even in low doses) is a specific and selective inhibitor of MMP activity and thus can prevent extra-cellular matrix destruction. We propose to test the hypothesis that endothelial function in subjects with various degrees of endothelial dysfunction will be impoved following administration of low dose doxycycline.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。基质金属蛋白酶 9 (MMP-9) 被发现在动脉粥样硬化斑块中具有酶活性。在从不稳定型心绞痛患者的“罪魁祸首”冠状动脉病变中获取的标本中，83% 都发现了这种物质。据报道，急性冠状动脉综合征患者的 MMP-9 水平也升高。这些发现提出了这样的可能性：MMP-9抑制剂可能为稳定冠状动脉疾病患者的动脉粥样硬化病变和预防急性缺血综合征提供一种新的治疗方法。强力霉素（即使是低剂量）是一种特异性、选择性的 MMP 活性抑制剂，因此可以防止细胞外基质破坏。我们建议检验以下假设：具有不同程度内皮功能障碍的受试者的内皮功能在给予低剂量多西环素后会得到改善。