MATRIX METALLOPROTEINASES ON ENDOTHELIAL FUNCTION IN ATHEROSCLEROSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。基质金属蛋白酶-9（MMP-9）已被发现在动脉粥样硬化斑块中具有酶活性。从不稳定型心绞痛患者的“罪犯”冠状动脉病变中获得的样本中发现了83%。在急性冠状动脉综合征患者中也有MMP-9水平升高的报道。这些发现提出了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新的治疗形式的可能性。多西环素（即使在低剂量下）是MMP活性的特异性和选择性抑制剂，因此可以防止细胞外基质破坏。我们建议测试的假设，即在不同程度的内皮功能障碍的受试者将改善后，给予低剂量的多西环素。

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.