Piezo1-mediated mechanical signaling in cardiovascular regulation
Mechanical signaling plays a crucial role in cardiovascular physiology and pathology.Piezo1,the first mechanosensitive cation channel protein discovered in mammals,acts as a cell membrane mechanoreceptor.It primarily triggers downstream signaling pathways by facilitating Ca2+influx.In cardiomyocytes,Piezo1 senses tension changes during cardiac contraction and relaxation,regulating cardiac contractility.Endothelial cell Piezo1 responds to shear stress from blood flow,contributing to vascular development and functional regulation.In vascular smooth muscle cells,Piezo1 senses tension changes caused by blood pressure,leading to vascular structural and functional remodeling.Dysregulated Piezo1 expression or activation disrupt myocardial Ca2+homeostasis,and correlates with various cardiovascular diseases such as cardiac fibrosis,atherosclerosis,and vascular aging.Exercise-induced changes in blood flow velocity activate endothelial cell Piezo1,promoting Na+and Ca2+influx,causing endothelial cell depolarization.This depolarization signal is transmitted via gap junctions to adjacent smooth muscle cells,inducing mesenteric resistance vessel contraction and blood flow redistribution during exercise.Our previous study suggests that fluid redistribution due to simulated microgravity increases carotid artery smooth muscle tension,activating Piezo1 and leading to vascular remodeling and aging.This finding indicates that Piezo1 may be involved in the gravity sensing process under weightlessness conditions.Notably,the biological effects induced by Piezol activation vary with intensity,type,or duration of mechanical stimuli.Further elucidation of the activation mechanisms and biological functions of Piezo1 under different mechanical stimuli could provide new insights for the prevention and treatment of cardiovascular diseases.
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