Cell-based therapy for atherosclerosis is emerging as a viable treatment strategy. Endothelial progenitor cells (EPCs) are key mediators of the repair process however its regulatory mechanisms are poorly understood. We propose to investigate the role of the endothelial receptor tyrosine kinase Tie2 in the regulation of EPC physiology. We hypothesize that Tie2 is required for EPC-mediated vascular repair in atherosclerosis and that Ang2, but not Ang1, will enhance EPC repair of atherosclerotic lesions. The Specific Aims of this proposal are to: 1. Determine whether inhibition of Tie2 signaling will alter EPC number and survival. 2. Evaluate the effects of angiopoietin-1 (Ang1) or angiopoietin-2 (Ang2) on EPC number and survival. 3. Investigate whether inhibition of Tie2 signaling or overexpression of the angiopoietins alters EPC homing to and the prevention of atherosclerotic lesions. Accomplishing these Specific Aims may provide novel insights into the regulation of EPC-mediated repair, and may enhance the efficacy of cell-based therapies for athersclerosis and other vascular diseases.
NIH ExPorter
NIH ExPorter