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(EPC)是修复过程中的关键介质，但其调控机制尚不清楚。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Tie2是动脉粥样硬化中内皮祖细胞介导的血管修复所必需的，并且Ang2而不是Ang1将促进动脉粥样硬化病变的EPC修复。这项建议的具体目的是： 1.确定抑制Tie2信号是否会改变内皮祖细胞的数量和存活率。 2.评价血管生成素-1(Ang1)或血管生成素-2(Ang2)对内皮祖细胞数量和存活的影响。 3.研究抑制Tie2信号转导或血管生成素过度表达是否改变了EPC的归巢和动脉粥样硬化病变的预防。 实现这些特定的目标可能为调节EPC介导的修复提供新的见解，并可能增强基于细胞的治疗动脉粥样硬化和其他血管疾病的疗效。

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.