Mechanosensing and Mechanoregulation of Endothelial Cell Functions
Mechanosensing and Mechanoregulation of Endothelial Cell Functions
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DOI：
10.1002/cphy.c180020
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发表时间：
2019-04-01
影响因子：
5.8
通讯作者：
Birukov, Konstantin G.
中科院分区：
文献类型：
--
作者：
Fang, Yun;Wu, David;Birukov, Konstantin G.
血管内皮细胞（EC）对大分子和细胞成分形成半选择性屏障，受细胞骨架成分和细胞粘附复合物之间动态相互作用的调节。内皮细胞还参与许多其他重要过程，包括先天免疫反应、血管修复、分泌和生物活性分子的代谢。此外，血管EC代表了暴露于连续的、时间依赖性机械力的独特细胞类型：由大血管系统中的血流和由微血管系统中的滚动血细胞施加的不同模式的剪切应力;由心脏推进引起的动脉血管床经历的周向周期性拉伸;危重患者中由于自主呼吸或机械通气导致的不同程度的肺微血管内皮的机械拉伸。越来越多的证据表明，血管内皮细胞含有机械感觉复合体，它能迅速对机械负荷的变化做出反应，处理信号，并产生特定的适应性反应，以重新平衡细胞的稳态。EC微环境中特定机械力与循环生物活性分子之间的相互作用在血管病变（包括血管损伤、动脉粥样硬化、肺水肿和急性呼吸窘迫综合征）的进展和解决中的重要性最近才被认识到。本文将总结目前的EC mechanosensory机制的理解，调节EC的体液因素周围的机械力（特别是循环拉伸），并讨论了最近的研究结果的幅度特异性调节EC功能的转录，转录后和表观遗传机制，使用组学方法。我们还讨论了目前的挑战和未来的机会，在开发新的治疗靶向失调的机械感应机制，以治疗血管疾病。(C)2019美国生理学会
Vascular endothelial cells (ECs) form a semiselective barrier for macromolecules and cell elements regulated by dynamic interactions between cytoskeletal elements and cell adhesion complexes. ECs also participate in many other vital processes including innate immune reactions, vascular repair, secretion, and metabolism of bioactive molecules. Moreover, vascular ECs represent a unique cell type exposed to continuous, time-dependent mechanical forces: different patterns of shear stress imposed by blood flow in macrovasculature and by rolling blood cells in the microvasculature; circumferential cyclic stretch experienced by the arterial vascular bed caused by heart propulsions; mechanical stretch of lung microvascular endothelium at different magnitudes due to spontaneous respiration or mechanical ventilation in critically ill patients. Accumulating evidence suggests that vascular ECs contain mechanosensory complexes, which rapidly react to changes in mechanical loading, process the signal, and develop context-specific adaptive responses to rebalance the cell homeostatic state. The significance of the interactions between specific mechanical forces in the EC microenvironment together with circulating bioactive molecules in the progression and resolution of vascular pathologies including vascular injury, atherosclerosis, pulmonary edema, and acute respiratory distress syndrome has been only recently recognized. This review will summarize the current understanding of EC mechanosensory mechanisms, modulation of EC responses to humoral factors by surrounding mechanical forces (particularly the cyclic stretch), and discuss recent findings of magnitude-specific regulation of EC functions by transcriptional, posttranscriptional and epigenetic mechanisms using -omics approaches. We also discuss ongoing challenges and future opportunities in developing new therapies targeting dysregulated mechanosensing mechanisms to treat vascular diseases. (C) 2019 American Physiological Society.