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.
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