title: Arterial Myogenic Activation through Smooth Muscle Filamin A.
abstract: Mutations in the filamin A (FlnA) gene are frequently associated with severe arterial abnormalities, although the physiological role for this cytoskeletal element remains poorly understood in vascular cells. We used a conditional mouse model to selectively delete FlnA in smooth muscle (sm) cells at the adult stage, thus avoiding the developmental effects of the knockout. Basal blood pressure was significantly reduced in conscious smFlnA knockout mice. Remarkably, pressure-dependent tone of the resistance caudal artery was lost, whereas reactivity to vasoconstrictors was preserved. Impairment of the myogenic behavior was correlated with a lack of calcium influx in arterial myocytes upon an increase in intraluminal pressure. Notably, the stretch activation of CaV1.2 was blunted in the absence of smFlnA. In conclusion, FlnA is a critical upstream element of the signaling cascade underlying the myogenic tone. These findings allow a better understanding of the molecular basis of arterial autoregulation and associated disease states.
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: Malika
authors.initials: M
authors.lastname: Arhatte
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.
authors.forename: Rémi
authors.initials: R
authors.lastname: Peyronnet
authors.affiliation: INSERM U970, PARCC-Université Paris Descartes-Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudrie
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: CNRS UMR 6214, INSERM U1083, CARFI Facility and Université d'Angers, 49045 Angers Cédex 01, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bourreau
authors.affiliation: CNRS UMR 6214, INSERM U1083, CARFI Facility and Université d'Angers, 49045 Angers Cédex 01, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
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: Division of Translational Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
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: 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.
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. Electronic address: honore@ipmc.cnrs.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D020013:Calcium Signaling; D002478:Cells, Cultured; D005260:Female; D064448:Filamins / Q000502:physiology*; D007668:Kidney / Q000098:blood supply; D008297:Male; D040542:Mechanotransduction, Cellular; D018345:Mice, Knockout; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology
chemical_list: D064448:Filamins