Fig. 7

Role of the Piezo1 channel in vascular development and tone. a In blood vessels, shear stress (laminar flow: blue arrow) triggered Piezo1-mediated Ca²⁺ influx and thereby facilitated endothelial cell (EC) alignment via the regulation of focal adhesions and EC sprout formation via the activation of MT1-MMP signaling. b In blood vessels, shear stress (laminar flow: blue arrow) activated the Piezo1 channel in ECs and subsequently mediated vascular tone. Specifically, shear stress led to Piezo1-dependent adrenomedullin release in ECs, which then activated the G_s-coupled endothelial adrenomedullin receptor. The subsequent increase in cAMP levels promoted the phosphorylation of endothelial NO synthase (eNOS) and caused NO production and vasodilation. Additionally, shear stress activated the Piezo1 channel in ECs and subsequently mediated the release of ATP in part by pannexin channels. Extracellular ATP, in turn, stimulated G_q/G₁₁-coupled purinergic P2Y2 receptors, resulting in the phosphorylation of eNOS via PI3K/AKT signaling and increased NO formation