Piezo1 in atherosclerosis: a multifaceted mechanosensor bridging mechanotransduction, inflammation, and emerging therapies
- 1School of Clinical Medicine, Southwest Medical University
- 2Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University
- 3Key Laboratory of Cardiovascular Remodeling and Dysfunction
Abstract
The pathogenesis of atherosclerosis is closely associated with dysregulated mechanosensation mediated by the Piezo1 channel. Piezo1 is expressed in vascular endothelial cells, smooth muscle cells, macrophages, and neutrophils, where it transduces hemodynamic shear stress (e.g., oscillatory shear stress, OSS) and extracellular matrix stiffness into pathological signals. At the molecular level, Piezo1 drives endothelial inflammation through the Ca ²⁺ /calmodulin (CaM)/calcium/calmodulin-dependent protein kinase II (CaMKII)-focal adhesion kinase (FAK)/Src-Yes-associated protein (YAP) axis, promotes vascular smooth muscle cell pyroptosis and calcification via the Ca ²⁺ -CaMKII-NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathway. In addition, Piezo1 contributes to inflammatory responses through the Piezo1-Src-signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, low shear stress-induced NETosis is mediated by the Piezo1-histone deacetylase 2 (HDAC2) axis, in which Piezo1 downregulation leads to HDAC2 upregulation. At the cellular level, Piezo1 participates in regulating endothelial mechanotransduction, smooth muscle cell phenotypic switching, and macrophage functional polarization and foam cell formation in a context-dependent manner, ultimately affecting plaque stability. Piezo1 activity is subject to positive regulation by mechanical stimuli, chemical agonists (Yoda1), and pathological factors [such as the G protein-coupled receptor 146 (GPR146)-cAMP-CREB1 axis], as well as negative regulation by GsMTx4 and various natural compounds [salvianolic acid B, hydroxysafflor yellow A (HysA), and kaempferol]. This review systematically delineates the multicellular roles of Piezo1 throughout the full course of atherosclerosis and its integration with inflammatory and metabolic responses, providing a theoretical foundation for targeted intervention strategies. Future research should focus on the development of highly selective modulators, optimization of cell-specific delivery systems, and systematic integration of mechanotransduction with inflammatory and metabolic pathways.
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BibTeX
@article{liu2026piezo1,
title = {{Piezo1 in atherosclerosis: a multifaceted mechanosensor bridging mechanotransduction, inflammation, and emerging therapies}},
author = {Tianrui Liu and Yongmei Nie},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1979257},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1979257/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Piezo1 in atherosclerosis: a multifaceted mechanosensor bridging mechanotransduction, inflammation, and emerging therapies
AU - Tianrui Liu
AU - Yongmei Nie
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1979257
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1979257/full
AB - The pathogenesis of atherosclerosis is closely associated with dysregulated mechanosensation mediated by the Piezo1 channel. Piezo1 is expressed in vascular endothelial cells, smooth muscle cells, macrophages, and neutrophils, where it transduces hemodynamic shear stress (e.g., oscillatory shear stress, OSS) and extracellular matrix stiffness into pathological signals. At the molecular level, Piezo1 drives endothelial inflammation through the Ca ²⁺ /calmodulin (CaM)/calcium/calmodulin-dependent protein kinase II (CaMKII)-focal adhesion kinase (FAK)/Src-Yes-associated protein (YAP) axis, promotes vascular smooth muscle cell pyroptosis and calcification via the Ca ²⁺ -CaMKII-NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathway. In addition, Piezo1 contributes to inflammatory responses through the Piezo1-Src-signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, low shear stress-induced NETosis is mediated by the Piezo1-histone deacetylase 2 (HDAC2) axis, in which Piezo1 downregulation leads to HDAC2 upregulation. At the cellular level, Piezo1 participates in regulating endothelial mechanotransduction, smooth muscle cell phenotypic switching, and macrophage functional polarization and foam cell formation in a context-dependent manner, ultimately affecting plaque stability. Piezo1 activity is subject to positive regulation by mechanical stimuli, chemical agonists (Yoda1), and pathological factors [such as the G protein-coupled receptor 146 (GPR146)-cAMP-CREB1 axis], as well as negative regulation by GsMTx4 and various natural compounds [salvianolic acid B, hydroxysafflor yellow A (HysA), and kaempferol]. This review systematically delineates the multicellular roles of Piezo1 throughout the full course of atherosclerosis and its integration with inflammatory and metabolic responses, providing a theoretical foundation for targeted intervention strategies. Future research should focus on the development of highly selective modulators, optimization of cell-specific delivery systems, and systematic integration of mechanotransduction with inflammatory and metabolic pathways.
SN - 2297-055X
ER -