The Role of Tie2 and the Angiopoietins in EPC Biology

描述（由申请人提供）：基于细胞的动脉粥样硬化治疗正在成为一种可行的治疗策略。内皮祖细胞（EPCs）是修复过程的关键介质，但其调节机制尚不清楚。我们建议研究内皮受体酪氨酸激酶Tie2在EPC生理调节中的作用。我们假设动脉粥样硬化中EPC介导的血管修复需要Tie2，而Ang2而不是Ang1会增强EPC对动脉粥样硬化病变的修复。本建议的具体目标是：

DESCRIPTION (provided by applicant): 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.