张应变调控的内皮祖细胞能量代谢参与血管内皮损伤修复的力学生物学机制

内皮祖细胞（EPCs）可分化为成熟内皮细胞，在血管损伤修复和维持血管稳态中发挥重要作用。周期性张应变条件下，EPCs能量代谢参与调控EPCs功能及血管损伤修复的机制尚不清楚。本研究拟采用周期性张应变加载系统，应用代谢组学和蛋白质组学技术，筛选静态条件和生理性张应变条件下EPCs差异表达的代谢物和蛋白质，构建参与调控能量代谢的通路图谱；细胞实验验证EPCs能量代谢变化，探讨能量代谢关键调节蛋白影响EPCs功能的机制；构建颈动脉内膜损伤模型，验证能量代谢关键调节蛋白在EPCs修复损伤血管内膜中的作用；并构建能量代谢关键调节蛋白的转基因小鼠（或基因敲除鼠），进一步明确该关键调节蛋白在EPCs参与血管损伤修复中的作用。本项目旨在阐明力学因素通过能量代谢途径调控EPCs功能的机制，为筛选以能量代谢关键调节蛋白为靶点的相关疾病防治提供力学生物学依据。

Endothelial progenitor cells (EPCs) can differentiate into mature endothelial cells (ECs), and participate in the reendothelialization of vascular injury and maintain the vascular homeostasis. How EPC energy metabolism and its key regulator proteins mediate EPC function and intimal injury repair under cyclic stretch, the mechanism is still unclear. In the current project, by using FX-5000T Strain Unit (Flexcell International) system, metabolomics and proteomics, the differential expressed metabolites and proteins in EPCs loaded with or without physiological cyclic stretch are screened, which construct the network of EPC energy metabolism. EPC energy metabolism functions are validated under cyclic stretch and the key regulator proteins involved in EPC function are selected. The effect of key energy metabolism regulator proteins and the underlying mechanism on EPC function and reendothelialization are investigated by the establishment of rat vascular injury model. The transgenic mice and knock-out mice are constructed to verify the role of energy metabolism regulator proteins in EPC function and reendothelialization. The aim of the current study is to understand the mechanism of how cyclic stretch mediates EPC fate by regulating its energy metabolism and to verify the key energy metabolism regulator proteins. It provides some new insights into mechanotransduction of EPC energy metabolism and functions for the clinical therapy.