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疗法正在成为一种可行的治疗策略。内皮祖细胞（EPC）是修复过程的关键介质，但对其调节机制知之甚少。我们拟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 EPC 介导的动脉粥样硬化血管修复所必需的，并且 Ang2（而非 Ang1）将增强动脉粥样硬化病变的 EPC 修复。该提案的具体目标是： 1. 确定抑制 Tie2 信号传导是否会改变 EPC 数量和存活率。 2. 评估血管生成素-1 (Ang1) 或血管生成素-2 (Ang2) 对 EPC 数量和存活率的影响。 3. 研究抑制 Tie2 信号传导或过度表达血管生成素是否会改变 EPC 归巢并预防动脉粥样硬化病变。 实现这些具体目标可能会为 EPC 介导的修复调节提供新的见解，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功效。

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.