BMP4在调控衰老内皮祖细胞血管内皮损伤修复中的作用及机制研究

衰老导致动脉内皮损伤，循环内皮祖细胞迁移、归巢并定植到损伤部位，从而加速损伤动脉再内皮化，是修复内皮损伤和维持血管内皮结构与功能完整的关键。我们以前的研究表明衰老导致循环内皮祖细胞数量和功能明显下降，然衰老对内皮祖细胞再内皮化的影响及分子机制尚不明了。本课题采用细胞生物学、分子生物学、免疫组织化学、血管病理学、生物力学、基因转染及siRNA 干扰等多学科交叉方法，从体外细胞培养模型、动物血管损伤修复模型以及整体运动模型三方面，研究BMP4信号通路与衰老内皮祖细胞血管内皮损伤修复能力的关系，探讨体外切应力和在体运动改善衰老内皮祖细胞再内皮化能力的可行性及分子机制。首次提出BMP4信号通路受损是衰老内皮祖细胞血管内皮损伤修复能力减弱的关键环节之一，为运动作为生活方式干预防治动脉血管疾病提供新的分子生物学理论依据和应用基础。

Aging is a well-recognized risk factor for vascular endothelium injury. Circulating endothelial progenitor cell (EPCs) accelarating the reendothelialization of injured vascular though homing and planting to the injured sites is the key link of endothelial injury repair, vascular endothelium structural and functional intact. Our previous studies indicated that aging impaired the number and function of circulating EPCs. At present, studies about the effect and molecular mechanism of aging on the reendothelialiation capacity of EPCs are not reported. The study will construct the experimental model of cell culture in vivo, animal vascular injured model and clinical model via multidisciplinary techniques such as cytobiology molecular, histochemistry pathology, RNA interference and so on, to investigate the relation of bone morphogenetic protein 4 (BMP4) signal pathway and aged-related vascular endothelial injury. Then, the study try to demonstrate the feasibility and underling mechanism of shear stress in vitro and exercise in vivo restoring the aging-induced decrease on the reendothelialization capacity of EPCs. The study first put forward the downregulated BMP4 signaling may be one of underling mechanism contribute to the impaired vascular endothelium repair capacity of EPCs from aging person, and may provide a new molecular biology theoretical basis and clinical practice foundation for exercise-mediated EPCs in prevention and treatment of atherosclerosis vascular diseases.