EPC mediated Neovascularization in Ischemic Myocardium

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DESCRIPTION (provided by applicant): Ischemic cardiomyopathy (ICM) is an increasingly prevalent global health concern. Endothelial progenitor cell (EPC) mediated neo-vascularization may provide a means to increase collateral circulation in ischemic myocardium, thereby improving cardiac function. A strategy of global bone marrow stimulation with granulocyte-monocyte colony stimulating factor (GM-CSF) to induce EPC proliferation combined with stromal cell-derived factor (SDF) targeted myocardial EPC chemokinesis will be utilized to enhance neovasculogenesis within ischemic myocardium. Initial data obtained utilizing an established rat model of ICM has demonstrated enhanced myocardial contractility and neovascularization among rats treated with a combination of GM-CSF and SDF. The proposed research will attempt to elucidate the role of SDF as a novel means of enhancing myocardial neovascularization specifically focusing on EPC mobilization, myocardial perfusion, ischemia reversal, enhanced myocardial function, and limited ventricular remodeling with preservation of geometry.