高血压机械力诱导血管平滑肌细胞结构与功能变化及其在血管疾病中的作用

The structural and functional changes of vascular smooth muscle cells induced by hypertensive mechanical forces and their roles in vascular diseases

血压升高产生的机械力在血管分化与发育、血管正常结构与功能维持以及血管病变过程中起决定作用,血脂和/或血糖异常升高可协同机械力作用加速血管重构及疾病发生发展。机械力可非特异性激活血管细胞所有跨膜蛋白分子,引起细胞内多信号通道分子(第二效应分子)同步活化。多通道信号分子在信号网络结点分子汇集,继而再散发,启动更多信号通路活化,实现信号的级联瀑布放大,导致细胞一系列病理生理学变化如细胞分化、迁移、炎症、表型变化、钙化、增殖、凋亡等,最终引起血管的结构与功能改变如动脉粥样硬化等,成为心脑血管疾病致死、致残的主要原因。本文对本课题组及国际同行相关研究进展,亦即血压升高产生的机械力对血管平滑肌细胞作用相关的血管重构做一简要综述。

The mechanical force caused by elevated blood pressure plays a decisive role in vascular differentiation and development,the maintenance of normal vascular structure and function,and the process of vascular lesions.Abnormal elevation of blood lipid and/or blood glucose synergistically accelerate mechanical force-initiated vascular remodeling and the occurrence and development of diseases.Mechanical forces can nonspecifically activate all transmembrane protein molecules in vascular cells,leading to simultaneous activation of intracellular multi-signal channel molecules(secondary effector molecules).The upstream multi-pathway molecular signals converge on the node molecules of signal network and then diverge to the downstream pathway molecules,and finally start more signaling pathway activation,and amplify the signal cascades.Then,a series of pathophysiological changes such as cell differentiation,migration,inflammation,phenotypic changes,calcification,proliferation,and apoptosis occur.Finally,the structural and functional changes of blood vessels,such as atherosclerosis,become the main cause of death and disability caused by cardiovascular and cerebrovascular diseases.This paper reviews the research progress from this research group and international peers,that is,vascular remodeling is closely related to the effect of mechanical force generated by elevated blood pressure on vascular smooth muscle cells.