血管支架植入对血管造成力学损伤，其再内皮化修复主要依赖于血管内皮细胞（VECs）迁移和内皮祖细胞（EPCs）归巢黏附，然而两种细胞参与再内皮化的协同作用及影响机制尚未明确。本项目拟采用优化的流动腔系统以及ApoE-/-转基因小鼠模型，体内外模拟支架扩张对血管的不同损伤程度；采用免疫荧光、β-gel标记等方法，实时观测再内皮化进程；测定PI3K/AKT/eNOS信号轴关键蛋白表达规律，明确EPCs、VECs之间的相互作用及共同参与再内皮化修复的力学生物学机制。从而回答以下科学问题：①参与支架段血管再内皮化修复的细胞主要来源于VECs还是EPCs？两者是否具有协同作用，各自贡献多少？②血流剪切力、血管损伤程度等不同影响因素如何介导VECs和EPCs的相互作用及再内皮化进程？③调控两者协同作用的分子机制？本项目研究结果有助于揭示血管修复的力学生物学机制，对心血管介入材料的设计改进具有重要的指导意义。

The implantation of vascular stent introduces a mechanical injure to vessle wall, and the subsequent re-endothlialzation process depends on both of the neighboring vascular endothelial cells (VECs) migration and circulating bone marrow-derived endothelial progenitor cells (EPCs) homing and adhesion. However, the synergistic effect and relative molecular mechanism of two cell population contribute to re-endothlialzation repair are unclear. In this project, the optimized flow chamber system and Tie2-Lac (Tie2-GFP) ApoE-/- transgentic mice were applied to simulate deep injure induced by stent implatation and expansion in vitro and in vivo. Also, the fluorescence labeling and β-gel staining were used to recognize VECs and EPCs, respecively, and to examine the time course of re-endothelialization. In addition, the expression levels and activated sequence of critical proteins in PI3K/AKT/eNOS signaling events would be studied to explore the mechanobiologic mechanism of synergistic effect of VECs and EPCs in re-endothlialzation process. We try to find the answers of the following questions: (1) what kind of endothelial cell repopulation mainly contributes to the stented re-endothelialization? Do adjacent VECs migration and circulating EPCs homing show a synergistic effect on the re-endothelialization repair? (2) How does the fluid shear stress induce the interaction between VECs and EPCs under the condition of deep injured blood vessel? (3) What’s mechanism in regulating synergistic effect of two endothelial cell populations? The finding of this project would help us to understand the mechanobiologic mechanism of re-endothelialization repair, and provide the sugestions for the design and improvement of cardiovascular implants.