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Etude physiopathologique du tonus myogénique vasculaire : implication de Rhoa, de Notch3 et du facteur de réponse au sérum.

Abstract : The myogenic tone (MT) is the ability of the resistance arteries to contract in response to an increase in intraluminal pressure. MT protects capillaries against excessive rises in pressure, and regulates local blood flow. Due to its role in the development of pathologies, MT is an interesting therapeutic target. However the molecular mechanisms involved in MT still remain to be elucidated. The RhoA/Rho-kinase pathway plays an important role in the MT in particular via its role in the calcium sensitization of the contractile apparatus. Thus, we were particularly interested in determining factors that can modulate or be modulated by this pathway. First, we demonstrated that MT requires RhoA to be localized at the cellular membrane, where it interacts with caveolin-1 and activates its effectors such as Rho-kinase. Furthermore the activation of RhoA by the pressure is regulated by the Notch3 receptor, so occurring as a mechanosensor. Our works also showed the role of the serum response factor (SRF) in the MT via the regulation of the cytoskeleton and the activity of mecanosensitive channels. Finally, we showed in sildenafil treated rats, that the inhibition of RhoA activity induced a overexpression of it, that is responsible to an increase of the MT and an hypertension after this treatment. These works bring new and additional knowledges on the implication of proteins such as RhoA, Notch3 and SRF in the MT providing a better understanding of this mechanism and its regulation. These new elements offer new therapeutic targets for the treatment of pathologies involving vascular dysfonctions.
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https://tel.archives-ouvertes.fr/tel-00536142
Contributor : Anne-Marie Plé <>
Submitted on : Sunday, January 1, 2012 - 7:00:11 AM
Last modification on : Friday, May 10, 2019 - 1:08:02 PM
Long-term archiving on: : Tuesday, December 13, 2016 - 6:26:55 PM

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  • HAL Id : tel-00536142, version 1

Citation

Kevin Retailleau. Etude physiopathologique du tonus myogénique vasculaire : implication de Rhoa, de Notch3 et du facteur de réponse au sérum.. Médicaments. Université d'Angers, 2010. Français. ⟨tel-00536142⟩

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