The Role of Tie2 and the Angiopoietins in EPC Biology

Tie2 和血管生成素在 EPC 生物学中的作用

• 批准号: 7105433
• 负责人: GREGORY K W LAM
• 金额: $ 5.5万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-18 至 2007-07-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105433
• 关键词: Adenoviridae; angiopoietins; atherosclerosis; biological signal transduction; bone marrow; cardiovascular disorder prevention; cardiovascular disorder therapy; cardiovascular transplantation; cell migration; cell population study; cell transplantation; disease /disorder model; enzyme activity; gene expression; genetically modified animals; immunofluorescence technique; kinase inhibitor; laboratory mouse; nonhuman therapy evaluation; postdoctoral investigator; protein tyrosine kinase; recombinant virus; regeneration; vascular endothelium

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.

描述（由申请人提供）：动脉粥样硬化的基于细胞的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，但其调控机制知之甚少。我们建议研究内皮细胞受体酪氨酸激酶Tie 2在EPC生理调节中的作用。我们假设Tie 2是动脉粥样硬化中EPC介导的血管修复所必需的，Ang 2而不是Ang 1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Tie 2信号传导的抑制是否会改变EPC数量和存活。 2.评估血管生成素-1（Ang 1）或血管生成素-2（Ang 2）对EPC数量和存活率的影响。 3.研究抑制Tie 2信号或过度表达血管生成素是否会改变EPC归巢和预防动脉粥样硬化病变。 实现这些特定目标可能为EPC介导的修复调节提供新的见解，并可能增强基于细胞的动脉粥样硬化和其他血管疾病治疗的疗效。