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      The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation

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          Abstract

          In recent years, cardiovascular health problems are becoming more and more serious. At the same time, mechanical stimulation closely relates to cardiovascular health. In this context, Piezo1, which is very sensitive to mechanical stimulation, has attracted our attention. Here, we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells, NO production, lipid metabolism, DNA damage protection, the development of new blood vessels and maturation, narrowing of blood vessels, blood pressure regulation, vascular permeability, insulin sensitivity, and maintenance of red blood cell function. Besides, Piezo1 may participate in the occurrence and development of atherosclerosis, diabetes, hypertension, and other cardiovascular diseases. It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health. On the one hand, the function of Piezo1 is necessary to maintain cardiovascular health; on the other hand, under some extreme mechanical stimulation, the overexpression of Piezo1 may bring adverse factors such as inflammation. Therefore, this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.

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          Most cited references110

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          Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

          Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.
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            Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.

            Mechanical stimuli drive many physiological processes, including touch and pain sensation, hearing, and blood pressure regulation. Mechanically activated (MA) cation channel activities have been recorded in many cells, but the responsible molecules have not been identified. We characterized a rapidly adapting MA current in a mouse neuroblastoma cell line. Expression profiling and RNA interference knockdown of candidate genes identified Piezo1 (Fam38A) to be required for MA currents in these cells. Piezo1 and related Piezo2 (Fam38B) are vertebrate multipass transmembrane proteins with homologs in invertebrates, plants, and protozoa. Overexpression of mouse Piezo1 or Piezo2 induced two kinetically distinct MA currents. Piezos are expressed in several tissues, and knockdown of Piezo2 in dorsal root ganglia neurons specifically reduced rapidly adapting MA currents. We propose that Piezos are components of MA cation channels.
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              Piezos are pore-forming subunits of mechanically activated channels

              Mechanotransduction plays a crucial role in physiology. Biological processes including sensing touch and sound waves require yet unidentified cation channels that detect pressure. Mouse piezo1 (mpiezo1) and mpiezo2 induce mechanically activated cationic currents in cells; however, it is unknown if piezos are pore-forming ion channels or modulate ion channels. We show that Drosophila piezo (dpiezo) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. mpiezo1 assembles as a ~1.2 million-Dalton tetramer, with no evidence of other proteins in this complex. Finally, purified mpiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium red-sensitive ion channels. These data demonstrate that piezos are an evolutionarily conserved ion channel family involved in mechanotransduction.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                05 September 2022
                September 2023
                05 September 2022
                : 10
                : 5
                : 1956-1968
                Affiliations
                [a ]Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
                [b ]Department of Vascular & Intervention, Tenth Peoples' Hospital of Tongji University, Shanghai 200072, China
                [c ]School of Medicine, Chongqing University, Chongqing 400030, China
                Author notes
                []Corresponding author. wanggx@ 123456cqu.edu.cn
                [∗∗ ]Corresponding author. tieying_yin@ 123456cqu.edu.cn
                Article
                S2352-3042(22)00236-7
                10.1016/j.gendis.2022.08.015
                10363580
                37492728
                a0af9e9e-c056-40dc-a42d-872ddcfc897f
                © 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 3 November 2021
                : 12 August 2022
                Categories
                Review Article

                atherosclerosis,cardiovascular disease,endothelial cells (ecs),mechanical stimulation,piezo1

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