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16 results on '"Domenga, Valérie"'

10. Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries

Author

Belin De Chantemèle, Eric, 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), and ANR-05-MRAR-0011,CADASIL,Démence CADASIL : de l'exploration des mécanismes physiopathogéniques à l'évaluation de stratégies thérapeutiques(2005)

Subjects
MESH: Phenylephrine, local blood flow regulation, MESH: Acetylcholine, MESH: Pyridines, MESH: Tail, MESH: Vascular Resistance, resistance arteries, MESH: rho GTP-Binding Proteins, MESH: Amides, MESH: Mice, Knockout, MESH: Male, myogenic tone, MESH: Vasodilation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Enzyme Inhibitors, Notch receptors, flow-mediated dilation, MESH: Vasoconstriction, MESH: Animals, MESH: rho-Associated Kinases, MESH: Receptors, Notch, MESH: Arteries, MESH: Mice, MESH: Cerebral Arteries
Abstract

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.

Published
2008

11. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells

Author

Domenga, Valérie, primary, Fardoux, Peggy, additional, Lacombe, Pierre, additional, Monet, Marie, additional, Maciazek, Jacqueline, additional, Krebs, Luke T., additional, Klonjkowski, Bernard, additional, Berrou, Eliane, additional, Mericskay, Matthias, additional, Li, Zhen, additional, Tournier-Lasserve, Elisabeth, additional, Gridley, Thomas, additional, and Joutel, Anne, additional

Published
2004
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14. Notch3 Mutations in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a Mendelian Condition Causing Stroke and Vascular Dementia

Author

JOUTEL, ANNE, primary, CORPECHOT, CHRISTOPHE, additional, DUCROS, ANNE, additional, VAHEDI, KATAYOUN, additional, CHABRIAT, HUGUES, additional, MOUTON, PHILIPPE, additional, ALAMOWITCH, SONIA, additional, DOMENGA, VALÉRIE, additional, CÉCILLION, MICHAELLE, additional, MARÉCHAL, EMMANUELLE, additional, MACIAZEK, JACQUELINE, additional, VAYSSIÈRE, CÉLINE, additional, CRUAUD, CORINNE, additional, CABANIS, EMMANUEL-ALAIN, additional, RUCHOUX, MARIE MADELEINE, additional, WEISSENBACH, JEAN, additional, BACH, JEAN FRANÇOIS, additional, BOUSSER, MARIE GERMAINE, additional, and TOURNIER-LASSERVE, ELISABETH, additional

Published
1997
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15. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia

Author

Joutel, Anne, primary, Corpechot, Christophe, additional, Ducros, Anne, additional, Vahedi, Katayoun, additional, Chabriat, Hugues, additional, Mouton, Philippe, additional, Alamowitch, Sonia, additional, Domenga, Valérie, additional, Cécillion, Michaelle, additional, Maréchal, Emmanuelle, additional, Maciazek, Jacqueline, additional, Vayssière, Céline, additional, Cruaud, Corinne, additional, Cabanis, Emmanuel-Alain, additional, Ruchoux, Marie Madeleine, additional, Weissenbach, Jean, additional, Bach, Jean François, additional, Bousser, Marie Germaine, additional, and Tournier-Lasserve, Elisabeth, additional

Published
1996
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16. Notch3Mutations in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a Mendelian Condition Causing Stroke and Vascular Dementia

Author

JOUTEL, ANNE, CORPECHOT, CHRISTOPHE, DUCROS, ANNE, VAHEDI, KATAYOUN, CHABRIAT, HUGUES, MOUTON, PHILIPPE, ALAMOWITCH, SONIA, DOMENGA, VALÉRIE, CÉCILLION, MICHAELLE, MARÉCHAL, EMMANUELLE, MACIAZEK, JACQUELINE, VAYSSIÈRE, CÉLINE, CRUAUD, CORINNE, CABANIS, EMMANUEL-ALAIN, RUCHOUX, MARIE MADELEINE, WEISSENBACH, JEAN, BACH, JEAN FRANÇOIS, BOUSSER, MARIE GERMAINE, and TOURNIER-LASSERVE, ELISABETH

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited condition whose key features include recurrent subcortical ischemic events, migraine attacks and vascular dementia in association with diffuse white-matter abnormalities seen on neuroimaging. Pathologic examination shows multiple small deep cerebral infarcts, a leukoencephalopathy and a nonatherosclerotic nonamyloid angiopathy involving mainly the media of small cerebral arteries. To progress in understanding the pathophysiological mechanisms of this condition, we undertook the identification of the mutated gene. We mapped the CADASIL gene on chromosome 19p13.1. More than 120 families have been referred to our lab. Genetic linkage analysis of 33 of these families allowed us to reduce the size of the genetic interval to less than 1 cM and to demonstrate the genetic homogeneity of this condition. In the absence of any candidate gene, we undertook positional cloning of this gene. We identified, within the CADASIL critical region, the human Notch3gene, whose sequence analysis revealed deleterious mutations in CADASIL families co-segregating with the affected phenotype. These data establish that this gene causes CADASIL. Identification of the CADASIL gene will provide a valuable diagnostic tool for clinicians and could be used to estimate the prevalence of this underdiagnosed condition. It should help in the understanding of pathophysiological mechanisms of CADASIL and vascular dementia.

Published
1997
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