血流剪切应力与内皮细胞命运

Hemodynamic Shear Stress and Endothelial Cell Fate

血管发育和稳态维持以及血管病理进程均依赖于血管内衬的内皮细胞(endothelial cells,ECs)。ECs与血液直接接触并受到血流剪切应力的作用,血流剪切应力通过调控ECs的发育和细胞命运等生物学过程来调节血管稳态。ECs命运转化主要包括生理条件下通过内皮-造血干细胞转化(endothelial-to-hematopoietic transition,EHT)产生造血干/祖细胞进入循环系统,以及病理条件下经内皮-间充质转化(endothelial-to-mesenchymal transition,EndMT)形成间充质细胞参与血管狭窄等,这两种命运转化的共同特点之一是细胞间黏附分子和黏附力的破坏。本文旨在概述血流剪切应力调控内皮细胞EHT和EndMT的分子机制,将提升对心血管发育和相关疾病发生机制的理解。

Vascular endothelial cells(ECs),the inner layer of the blood vessels,are critical for vascular development,homeostasis maintenance,and pathological processes.ECs are subjected to hemodynamic shear stress due to their direct contact with blood,which regulates vascular homeostasis by modulating biological processes such as the development and cell fate of ECs.The cell fate transition of ECs mainly includes the generation of hematopoietic stem/progenitor cells that enter the circulatory system via endothelial-to-hematopoietic transition(EHT)and the formation of mesenchymal cells in vascular stenosis via endothelial-to-mesenchymal transition(EndMT)under pathological conditions.One common feature of both fate transitions is the disruption of intercellular adhesion.Here,we review the molecular mechanisms by which hemodynamic shear stress regulates EHT and EndMT in endothelial cells,providing valuable insights into the underlying mechanisms of cardiovascular development and related diseases.