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Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction

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dc.creator Sauzeau, Vincent
dc.creator Bustelo, Xosé R.
dc.date 2008-06-17T09:37:13Z
dc.date 2008-06-17T09:37:13Z
dc.date 2006-07
dc.date.accessioned 2017-01-31T01:42:19Z
dc.date.available 2017-01-31T01:42:19Z
dc.identifier Nature Medicine 12(7): 841–845 (2006)
dc.identifier 1078-8956
dc.identifier http://hdl.handle.net/10261/5128
dc.identifier 10.1038/nm1426
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5128
dc.description El pdf del artículo es el manuscrito de autor.-- et al.
dc.description Although much is known about environmental factors that predispose individuals to hypertension and cardiovascular disease, little information is available regarding the genetic and signaling events involved. Indeed, few genes associated with the progression of these pathologies have been discovered despite intensive research in animal models and human populations. Here we identify Vav3, a GDP-GTP exchange factor that stimulates Rho and Rac GTPases, as an essential factor regulating the homeostasis of the cardiovascular system.Vav3-deficient mice exhibited tachycardia, systemic arterial hypertension and extensive cardiovascular remodeling. These mice also showed hyperactivity of sympathetic neurons from the time of birth. The high catecholamine levels associated with this condition led to the activation of the renin-angiotensin system, increased levels of kidney-related hormones and the progressive loss of cardiovascular and renal homeostasis. Pharmacological studies with drugs targeting sympathetic and renin-angiotensin responses confirmed the causative role and hierarchy of these events in the development of theVav3-null mouse phenotype. These observations uncover the crucial role of Vav3 in the regulation of the sympathetic nervous system (SNS) and cardiovascular physiology, and reveal a signaling pathway that could be involved in the pathophysiology of human disease states involving tachycardia and sympathetic hyperactivity with unknown etiologies.
dc.description This work was supported by grants from the US National Institutes of Health to X.R.B. and the Spanish Ministry of Education and Science to X.R.B. and J.M.L.-N. V.S. is supported by a European Molecular Biology Organization (EMBO) longterm postdoctoral fellowship.
dc.description Peer reviewed
dc.format 22195 bytes
dc.format application/pdf
dc.language eng
dc.publisher Nature Publishing Group
dc.rights openAccess
dc.title Vav3 proto-oncogene deficiency leads to sympathetic hyperactivity and cardiovascular dysfunction
dc.type Artículo

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