Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

Abstract

Recently, more and more works have focused and used extensive resources on atherosclerosis research, which is one of the major causes of death globally. Alongside traditional risk factors, such as hyperlipidemia, smoking, hypertension, obesity, and diabetes, mechanical forces, including shear stress, pressure and stretches exerted on endothelial cells by flow, is proved to be crucial in atherosclerosis development. Studies have recognized the mechanosensitive Piezo1 channel as a special sensor and transducer of various mechanical forces into biochemical signals, and recent studies report its role in atherosclerosis through different mechanical forces in pressure, stretching and turbulent shear stress. Based on our expertise in this field and considering the recent advancement of atherosclerosis research, we will be focusing on the function of Piezo1 and its involvement in various cellular mechanisms and consequent involvement in the development of atherosclerosis in this review. Also, we will discuss various functions of Piezo1 involvement in atherosclerosis and come up with new mechanistic insight for future research. Based on the recent findings, we suggest Piezo1 as a valid candidate for novel therapeutic innovations, in which deep exploration and translating its findings into the clinic will be a new therapeutic strategy for cardiovascular diseases, particularly atherosclerosis.

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

“…Harmful mechanical force signals persist and damage tissues leading to chronic inflammatory diseases. Such as mechanical pressure overload leading to osteoarthritis and lumbar degeneration ( 6 , 7 ), disturbed haemodynamic shear forces damage vascular endothelial cells and ultimately lead to atherosclerosis ( 8 ), fat inflammation and insulin resistance induced by fat cell enlargement eventually progress to obesity and diabetes ( 9 ), overload of myocardium induces myocardial inflammation, which leads to long-term myocardial fibrosis and cardiac hypertrophy, etc. ( 10 ).…”

Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

“…44 The blood flow-induced hemodynamic changes regulate multiple signaling pathways in various vascular wall cells. [45][46][47] The recently reported signaling pathways related to the FSS mainly include vascular endothelial growth factor (VEGF), Notch, PDGF, Klf2, eNOS, endothelin, Rho family signaling molecules of TGFβ/ BMP/Smad pathway, MAPK signaling pathway, NF-κB signaling pathway, and GTPase signaling pathway. 48,49 When the cells receive the FSS mechanical signals, several mechanosensors will be triggered, including integrins, the glycocalyx, primary cilia, Gprotein-coupled receptors, and ion channels (K + , Ca 2+ ).…”

Endothelial Cell Plasma Membrane Biomechanics Mediates Effects of Pro-Inflammatory Factors on Endothelial Mechanosensors: Vicious Circle Formation in Atherogenic Inflammation

“…Piezo1 performs multiple roles in the cardiovascular system, and links mechanical stimuli to the triggering of both pro-and anti-atherogenic responses in ECs [138]. Piezo1 is expressed in many cell types participating in the development of atherosclerosis, including ECs, vascular smooth muscles cells, T and B cells, and monocytes, which undergo sequential transition into macrophages and lipid-engorged foam cells [138]. The endothelial-specific deletion of Piezo1 in mice impairs SS-mediated vascular development [131], sprouting angiogenesis, and vascular lumen formation [139].…”