Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling

The mechanically activated non-selective cation channel Piezo1 is a determinant of vascular architecture during early development. Piezo1-deficient embryos die at midgestation with disorganized blood vessels. However, the role of stretch-activated ion channels (SACs) in arterial smooth muscle cells in the adult remains unknown. Here, we show that Piezo1 is highly expressed in myocytes of small-diameter arteries and that smooth-muscle-specific Piezo1 deletion fully impairs SAC activity. While Piezo1 is dispensable for the arterial myogenic tone, it is involved in the structural remodeling of small arteries. Increased Piezo1 opening has a trophic effect on resistance arteries, influencing both diameter and wall thickness in hypertension. Piezo1 mediates a rise in cytosolic calcium and stimulates activity of transglutaminases, cross-linking enzymes required for the remodeling of small arteries. In conclusion, we have established the connection between an early mechanosensitive process, involving Piezo1 in smooth muscle cells, and a clinically relevant arterial remodeling. Piezo1 is a stretch-activated ion channel expressed in the endothelium and its deletion alters vascular architecture. However, its role in arterial myocytes remains unknown. Retailleau et al. show that smooth muscle Piezo1 is dispensable for the arterial myogenic tone but involved in the remodeling of small arteries upon hypertension. © 2015 The Authors.