MATRIX METALLOPROTEINASES ON ENDOTHELIAL FUNCTION IN ATHEROSCLEROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 基质金属蛋白酶-9(MMP9)在动脉粥样硬化斑块中具有酶活性。83%的标本来自不稳定型心绞痛患者冠脉病变的罪魁祸首。据报道，急性冠脉综合征患者中也有基质金属蛋白酶-9水平升高的报道。这些发现增加了一种可能性，即基质金属蛋白酶-9的抑制剂可能为稳定冠心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形式。多西环素(即使在低剂量下)是一种特异性和选择性的基质金属蛋白酶活性抑制剂，因此可以防止细胞外基质的破坏。我们建议对有不同程度内皮功能障碍的受试者使用小剂量多西环素后内皮功能得到改善的假设进行检验。

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.