Laboratory of Biomedical Engineering, School of Medicine, Dokkyo Medical University.
Laboratory of System Physiology, Department of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo.
Magn Reson Med Sci. 2022 Mar 1;21(2):258-266. doi: 10.2463/mrms.rev.2021-0018. Epub 2021 May 22.
Cells in the tissues and organs of a living body are subjected to mechanical forces, such as pressure, friction, and tension from their surrounding environment. Cells are equipped with a mechanotransduction mechanism by which they perceive mechanical forces and transmit information into the cell interior, thereby causing physiological or pathogenetic mechano-responses. Endothelial cells (ECs) lining the inner surface of blood vessels are constantly exposed to shear stress caused by blood flow and a cyclic strain caused by intravascular pressure. A number of studies have shown that ECs are sensitive to changes in these hemodynamic forces and alter their morphology and function, sometimes by modifying gene expression. The mechanism of endothelial mechanotransduction has been elucidated, and the plasma membrane has recently been shown to act as a mechanosensor. The lipid order and cholesterol content of plasma membranes change immediately upon the exposure of ECs to hemodynamic forces, resulting in a change in membrane fluidity. These changes in a plasma membrane's physical properties affect the conformation and function of various ion channels, receptors, and microdomains (such as caveolae and primary cilia), thereby activating a wide variety of downstream signaling pathways. Such endothelial mechanotransduction works to maintain circulatory homeostasis; however, errors in endothelial mechanotransduction can cause abnormalities in vascular physiological function, leading to the initiation and progression of various vascular diseases, such as hypertension, thrombosis, aneurysms, and atherosclerosis. Recent advances in detailed imaging technology and computational fluid dynamics analysis have enabled us to evaluate the hemodynamic forces acting on vascular tissue accurately, contributing greatly to our understanding of vascular mechanotransduction and the pathogenesis of vascular diseases, as well as the development of new therapies for vascular diseases.
活体组织和器官中的细胞会受到来自周围环境的机械力，如压力、摩擦力和张力。细胞配备有一种机械转导机制，通过该机制，它们可以感知机械力并将信息传递到细胞内部，从而引起生理或病理机械反应。内皮细胞（EC）排列在血管的内表面，它们会持续受到血流产生的切变应力和血管内压力产生的循环应变的影响。许多研究表明，EC 对这些血流动力变化敏感，并改变其形态和功能，有时通过修饰基因表达来实现。内皮细胞机械转导的机制已经阐明，最近发现质膜可以作为机械感受器。当 EC 暴露于血流动力时，质膜的脂质有序性和胆固醇含量会立即发生变化，导致膜流动性发生变化。这些质膜物理性质的变化会影响各种离子通道、受体和微区（如小窝和初级纤毛）的构象和功能，从而激活各种下游信号通路。这种内皮细胞机械转导有助于维持循环内稳态；然而，内皮细胞机械转导的错误会导致血管生理功能异常，从而引发各种血管疾病，如高血压、血栓形成、动脉瘤和动脉粥样硬化。详细的成像技术和计算流体动力学分析的最新进展使我们能够准确评估作用于血管组织的血流动力，这极大地促进了我们对血管机械转导和血管疾病发病机制的理解，以及为血管疾病开发新疗法。
