PIEZO Mechanotransduction in the Cardiovascular System: Physiological Roles and Disease Implications

ABSTRACT: Mechanotransduction is essential for cardiovascular physiology, enabling cells to sense and respond to mechanical forces such as shear stress, stretch, pressure, and extracellular matrix deformation. Among mechanosensitive ion channels, PIEZO1 and PIEZO2 have emerged as critical regulators of cardiovascular mechanobiology. These large trimeric ion channels convert mechanical stimuli into calcium-dependent electrochemical signals that regulate vascular development, endothelial homeostasis, cardiac remodeling, inflammatory activation, and blood pressure control. Recent advances in structural biology, electrophysiology, and molecular genetics have substantially improved understanding of PIEZO channel architecture, mechanogating mechanisms, and downstream signaling pathways. In the cardiovascular system, PIEZO1 functions prominently in endothelial cells, cardiomyocytes, fibroblasts, erythrocytes, and vascular smooth muscle cells, where dysregulated signaling contributes to hypertension, fibrosis, cardiac hypertrophy, ischemic injury, and vascular inflammation. This review summarizes current knowledge of PIEZO-mediated cardiovascular mechanotransduction, emphasizing structural mechanisms, physiological functions, disease implications, and therapeutic potential. Emerging computational approaches, including artificial intelligence and machine learning-assisted electrophysiology, are also discussed as promising tools for advancing mechanobiological research, multiscale modeling, and precision cardiovascular medicine.