PIEZO Force Sensors and the Heart

Abstract

The PIEZO1 and PIEZO2 membrane proteins form uniquely structured calcium permeable nonselective cation channels dedicated to mechanical force sensing in eukaryotic cells. In this review of the scientific literature, we address PIEZOs in the heart. PIEZOs enable the formation of the aortic valve, cardiac vasculature, and pericardial drainage. In the established heart, they enable baroreceptor pressure sensing and reflex regulation of the heart rate and influence the heart's size and stiffness through roles in cardiac myocytes and cardiac fibroblasts. Therefore, mechanical force sensing by PIEZOs participates in normal cardiac development and function. There is also interest in PIEZOs in pathophysiology, when the structure and mechanical properties of the heart often change. Studies in rats and mice suggest that experimentally induced cardiac stress and injury cause PIEZO upregulation that is adverse. Similar changes may occur in human heart disease, creating potential for therapeutic benefit through PIEZO modulation. This is a productive, accelerating, and exciting new research topic with importance for our understanding of the heart and its diseases.

Figure 1. PIEZO force sensors and the heart.

(A, upper) Cell-type locations of PIEZOs in and around the heart, including but not limited to endothelial cells, cardiac fibroblasts, cardiac myocytes, autonomic and sensory neurons, and blood cells such as red blood cells and monocytes. (Lower) Sketches of PIEZO channel indicating the activation by mechanical forces such as shear stress from fluid flow, membrane tension from cell stretch, and viscoelasticity from extracellular matrix stiffness. (B) Summary of the suggested physiological roles of PIEZOs in the heart including aortic valve formation, vascular formation, pericardial drainage, aortic baroreceptor pressure sensing and reflex regulation of blood pressure, protection from myopathy, and formation and regulation of extracellular matrix. (C) Summary of the suggested implications of altered PIEZO expression in pathophysiology including in reduced reflex regulation of heart rate and blood pressure, increased arrhythmia such as atrial fibrillation, hypertrophy, fibrosis, and adverse inflammation. (Figure created with BioRender.)