Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries. ; Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries.: Notch3 and vascular tone
In: ISSN: 1079-5642, 2008
Online
academicJournal
Zugriff:
International audience ; OBJECTIVE: Notch3, a member of the evolutionary conserved Notch receptor family, is primarily expressed in vascular smooth muscle cells. Genetic studies in human and mice revealed a critical role for Notch3 in the structural integrity of distal resistance arteries by regulating arterial differentiation and postnatal maturation. METHODS AND RESULTS: We investigated the role of Notch3 in vascular tone in small resistance vessels (tail and cerebral arteries) and large (carotid) arteries isolated from Notch3-deficient mice using arteriography. Passive diameter and compliance were unaltered in mutant arteries. Similarly, contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as dilation to acetylcholine or sodium nitroprusside were unaffected. However, Notch3 deficiency induced a dramatic reduction in pressure-induced myogenic tone associated with a higher flow (shear stress)-mediated dilation in tail and cerebral resistance arteries only. Furthermore, RhoA activity and myosin light chain phosphorylation, measured in pressurized tail arteries, were significantly reduced in Notch3KO mice. Additionally, myogenic tone inhibition by the Rho kinase inhibitor Y27632 was attenuated in mutant tail arteries. CONCLUSIONS: Notch3 plays an important role in the control of vascular mechano-transduction, by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone and flow-mediated dilation in the resistance circulation.
Titel: |
Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries. ; Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries.: Notch3 and vascular tone
|
---|---|
Autor/in / Beteiligte Person: | Belin de Chantemèle, Eric, J. ; Retailleau, Kevin ; Pinaud, Frédéric ; Vessières, Emilie ; Bocquet, Arnaud ; Guihot, Anne-Laure ; Lemaire, Barbara ; Domenga, Valérie ; Baufreton, Christophe ; Loufrani, Laurent ; Joutel, Anne ; Henrion, Daniel ; Biologie Neurovasculaire Intégrée (BNVI) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Service de chirurgie cardio-vasculaire et thoracique ; Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM) ; Genetique des Maladies Vasculaires ; Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; ANR-05-MRAR-0011,CADASIL,Démence CADASIL : de l'exploration des mécanismes physiopathogéniques à l'évaluation de stratégies thérapeutiques(2005) |
Link: | |
Zeitschrift: | ISSN: 1079-5642, 2008 |
Veröffentlichung: | HAL CCSD ; American Heart Association, 2008 |
Medientyp: | academicJournal |
DOI: | 10.1161/ATVBAHA.108.171751 |
Schlagwort: |
|
Sonstiges: |
|