title: Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling.
abstract: 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.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Retailleau
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Duprat
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Arhatte
authors.affiliation: Department of Molecular and Cellular Neuroscience, Howard Hughes Medical Institute, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Sanjeev Sumant
authors.initials: SS
authors.lastname: Ranade
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Peyronnet
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Joana Raquel
authors.initials: JR
authors.lastname: Martins
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Jodar
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Moro
authors.affiliation: Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: Department of Neurology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Demolombe
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France. Electronic address: patel@ipmc.cnrs.fr.
authors.forename: Amanda
authors.initials: A
authors.lastname: Patel
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France. Electronic address: honore@ipmc.cnrs.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: D007473:Ion Channels; C552920:Piezo1 protein, mouse; D011503:Transglutaminases; D002118:Calcium