- 著者
- Joji Ando Kimiko Yamamoto
- 出版者
- Japanese Society for Magnetic Resonance in Medicine
- 雑誌
- Magnetic Resonance in Medical Sciences (ISSN:13473182)
- 巻号頁・発行日
- pp.rev.2021-0018, (Released:2021-05-22)
- 参考文献数
- 96
- 被引用文献数
- 14
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.
- 著者
- Kimiko Yamamoto Joji Ando
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.82, no.11, pp.2691-2698, 2018-10-25 (Released:2018-10-25)
- 参考文献数
- 59
- 被引用文献数
- 26
Vascular endothelial cells (ECs) maintain circulatory system homeostasis by changing their functions in response to changes in hemodynamic forces, including shear stress and stretching. However, it is unclear how ECs sense changes in shear stress and stretching and transduce these changes into intracellular biochemical signals. The plasma membranes of ECs have recently been shown to respond to shear stress and stretching differently by rapidly changing their lipid order, fluidity, and cholesterol content. Such changes in the membranes’ physical properties trigger the activation of membrane receptors and cell responses specific to each type of force. Artificial lipid-bilayer membranes show similar changes in lipid order in response to shear stress and stretching, indicating that they are physical phenomena rather than biological reactions. These findings suggest that the plasma membranes of ECs act as mechanosensors; in response to mechanical forces, they first alter their physical properties, modifying the conformation and function of membrane proteins, which then activates downstream signaling pathways. This new appreciation of plasma membranes as mechanosensors could help to explain the distinctive features of mechanotransduction in ECs involving shear stress and stretching, which activate a variety of membrane proteins and multiple signal transduction pathways almost simultaneously.