Piezo ion channels in cardiovascular mechanobiology

Dominique Douguet (1) , Amanda Patel (1) , Aimin Xu (2) , Paul M Vanhoutte (2) , Eric Honoré (1)

1 IPMC - Institut de pharmacologie moléculaire et cellulaire
2 HKU - The University of Hong Kong

Mechanotransduction plays a key role in vascular development, physiology and disease states. Piezo1 is a mechanosensitive non-selective cationic channel present in endothelial and vascular smooth muscle cells. It is activated by shear stress associated with increases in local blood flow, as well as by cell membrane stretch upon elevation of blood pressure. Here we briefly review the pharmacological modulators of Piezo and discuss the present state of knowledge on the role of Piezo1 in vascular mechanobiology and associated clinical disorders, such as atherosclerosis and hypertension. Ultimately, we believe that this recent research will help identify novel therapeutic strategies for the treatment of vascular diseases. Blood flow generates a frictional force acting on the endothelium (shear stress, parallel to the vessel wall), as well as wall distension (stretch; a force perpendicular to the vessel wall) in response to changes in transmural pressure [1-4]. Shear stress can arise due to either laminar (smooth flow with fluid layers sliding in parallel) or turbulent (rough) flow of blood through the vasculature. These mechanical forces have a significant impact on vascular development, physiology and are implicated in various disease states, including atherosclerosis and hypertension [1-4]. Multiple mechanosensors (see Glossary) detect these mechanical forces within vascular cells, including elements of the extracellular matrix (ECM), adhesion molecules, the

Mots clés: vascular smooth muscle cells; baroreflex; blood pressure; endothelium; Piezo1; shear stress

Domaines: Pharmacologie

Dominique Douguet, Amanda Patel, Aimin Xu, Paul M Vanhoutte, Eric Honoré. Piezo ion channels in cardiovascular mechanobiology. Trends in Pharmacological Sciences, 2019, ⟨10.1016/j.tips.2019.10.002⟩. ⟨hal-02386137⟩