VEGF基因修饰的巨噬细胞对动脉粥样硬化早期血管内皮修复的作用及机制研究

Atherosclerosis is the usual cause of heart attacks, strokes even death. Endothelial injury or dysfunction has been proposed to be one of the initiating events of atherosclerosis. Endothelial progenitor cells (EPCs) play important roles in repair-to-injury of arteries. Many evidences have shown cardiovascular risk factors ,such as atherosclerosis, decrease the number and function of EPCs. In our study in 2011, we have demonstrated that VEGF-modified macrophages transdifferentiate into endothelial-like cells (ELCs) in vitro and in vivo. On that base, we plan to investigate if the VEGF-modified macrophages could repair the injured endothlium in early atherosclerosis. A model of vascular injury in early atherosclerosis is induced by Wire-injured carotid artery in ApoE-/- mice after 2 weeks with high-fat diet. Direct repair, promoting the chemotaxis and adhesion of EPCs, inhibiting of foam cells development, activating of TRPV1 and shift in subtype of monocytes and macrophages should be studied to investigate the repair mechanism. This study will try to demonstrate that VEGF-modified macrophages could repair endothelial cells after vascular injury in early atherosclerosis, which should supply a new method to prevent early atherosclerosis development.

动脉粥样硬化（AS）是严重危害人类健康的疾病。血管内皮损伤是AS的始发因素。针对损伤内皮的修复是防治AS的一大策略。内皮祖细胞（EPCs）被证实参与了内皮修复，但其在AS患者体内数量不足、功能降低严重阻碍了其疗效。在我们发现VEGF基因修饰的巨噬细胞可以转分化为内皮样细胞（2011年）的基础上，本项目拟用高脂饮食复制ApoE-/-小鼠AS模型，并行颈动脉球囊损伤，在体研究经人VEGF基因修饰的巨噬细胞对AS早期动脉内皮损伤的修复及AS斑块形成的影响。以直接修复、促进内皮祖细胞趋化、抑制泡沫细胞形成、调节单核-巨噬细胞的功能性分化、激活TRPV1的表达等为切入点，揭示VEGF基因修饰的巨噬细胞对AS早期动脉内皮损伤的修复机制。为"通过修复损伤的血管内皮来早期防治和阻止AS发展"的治疗策略提供新的思路和实验依据。