| Current coronary revascularization therapies confer higher risk and are less effective in metabolic syndrome patients. Therefore, effective and less invasive treat-ment options are needed for people suffering from metabolic syndrome and coronary artery disease (CAD). Coronary collateral growth (CCG) is an adaptive process in which small vessels remodel into larger conduit arteries, which allow for adequate blood flow to regions of the heart rendered ischemic by upstream occlusion of a major coronary artery, thus preventing myocardial infarction. CCG is however compromised in the metabolic syndrome. In order to utilize CCG as a non-invasive and effective revascularization alternative for CAD and prevention of myocardial infarction, the mechanisms of collateral growth and the reason(s) why it is compromised in the metabolic syndrome must be understood. This Dissertation explores the role of matrix metalloproteinases (MMPs) for CCG in the normal versus the metabolic syndrome phenotype. Specifically, in the first part of the dissertation I demonstrated that MMP 2 and 9 activation is required for CCG. In the second part, I demonstrated that MMP 12 inhibits CCG in the metabolic syndrome by generating anti-angiogenic peptides, angiostatin and endostatin. |
