Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells
- Autores
- Fabbiano, Salvatore; Menacho Márquez, Mauricio Ariel; Sevilla, María A.; Albarrán Juárez, Julián; Zheng, Yi; Offermanns, Stefan; Montero, María J.; Bustelo, Xosé R.
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically engineered mice to manipulate the signaling output of Rac1 in these cells at will using inducible, Cre-loxP-mediated DNA recombination techniques. Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic loss of wild-type Vav2. Conversely, the specific depletion of Rac1 in vSMCs causes defective nitric oxide vasodilation responses and hypertension. Rac1, but not Vav2, also is important for neointima formation but not for hypertension-driven vascular remodeling. These animals also have allowed us to dismiss etiological connections between hypertension and metabolic disease and, most importantly, identify pathophysiological programs that cooperate in the development and consolidation of hypertensive states caused by local vascular tone dysfunctions. Finally, our results suggest that the therapeutic inhibition of Rac1 will be associated with extensive cardiovascular system-related side effects and identify pharmacological avenues to circumvent them.
Fil: Fabbiano, Salvatore. Universidad de Salamanca; España
Fil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad de Salamanca; España
Fil: Sevilla, María A.. Universidad de Salamanca; España
Fil: Albarrán Juárez, Julián. Max-planck-instituts Für Herz- Und Lungenforschung; Alemania
Fil: Zheng, Yi. Cincinnati Children's Hospital Research Foundation; Estados Unidos
Fil: Offermanns, Stefan. Max-planck-instituts Für Herz- Und Lungenforschung; Alemania
Fil: Montero, María J.. Universidad de Salamanca; España
Fil: Bustelo, Xosé R.. Universidad de Salamanca; España - Materia
-
Rac1
Vav
GTPases
Signaling
vascular smooth muscle
Hypertension
Blood pressure
Nitric oxide, animal models
Nitric oxide
Animal models
Phosphodiesterase 5
Diabetes - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/95254
Ver los metadatos del registro completo
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Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cellsFabbiano, SalvatoreMenacho Márquez, Mauricio ArielSevilla, María A.Albarrán Juárez, JuliánZheng, YiOffermanns, StefanMontero, María J.Bustelo, Xosé R.Rac1VavGTPasesSignalingvascular smooth muscleHypertensionBlood pressureNitric oxide, animal modelsNitric oxideAnimal modelsPhosphodiesterase 5Diabeteshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically engineered mice to manipulate the signaling output of Rac1 in these cells at will using inducible, Cre-loxP-mediated DNA recombination techniques. Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic loss of wild-type Vav2. Conversely, the specific depletion of Rac1 in vSMCs causes defective nitric oxide vasodilation responses and hypertension. Rac1, but not Vav2, also is important for neointima formation but not for hypertension-driven vascular remodeling. These animals also have allowed us to dismiss etiological connections between hypertension and metabolic disease and, most importantly, identify pathophysiological programs that cooperate in the development and consolidation of hypertensive states caused by local vascular tone dysfunctions. Finally, our results suggest that the therapeutic inhibition of Rac1 will be associated with extensive cardiovascular system-related side effects and identify pharmacological avenues to circumvent them.Fil: Fabbiano, Salvatore. Universidad de Salamanca; EspañaFil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad de Salamanca; EspañaFil: Sevilla, María A.. Universidad de Salamanca; EspañaFil: Albarrán Juárez, Julián. Max-planck-instituts Für Herz- Und Lungenforschung; AlemaniaFil: Zheng, Yi. Cincinnati Children's Hospital Research Foundation; Estados UnidosFil: Offermanns, Stefan. Max-planck-instituts Für Herz- Und Lungenforschung; AlemaniaFil: Montero, María J.. Universidad de Salamanca; EspañaFil: Bustelo, Xosé R.. Universidad de Salamanca; EspañaAmerican Society for Microbiology2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95254Fabbiano, Salvatore; Menacho Márquez, Mauricio Ariel; Sevilla, María A.; Albarrán Juárez, Julián; Zheng, Yi; et al.; Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells; American Society for Microbiology; Molecular and Cellular Biology; 34; 24; 10-2014; 4404-44190270-7306CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/MCB.01066-14info:eu-repo/semantics/altIdentifier/doi/10.1128/MCB.01066-14info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:10Zoai:ri.conicet.gov.ar:11336/95254instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:06:10.661CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
title |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
spellingShingle |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells Fabbiano, Salvatore Rac1 Vav GTPases Signaling vascular smooth muscle Hypertension Blood pressure Nitric oxide, animal models Nitric oxide Animal models Phosphodiesterase 5 Diabetes |
title_short |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
title_full |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
title_fullStr |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
title_full_unstemmed |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
title_sort |
Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells |
dc.creator.none.fl_str_mv |
Fabbiano, Salvatore Menacho Márquez, Mauricio Ariel Sevilla, María A. Albarrán Juárez, Julián Zheng, Yi Offermanns, Stefan Montero, María J. Bustelo, Xosé R. |
author |
Fabbiano, Salvatore |
author_facet |
Fabbiano, Salvatore Menacho Márquez, Mauricio Ariel Sevilla, María A. Albarrán Juárez, Julián Zheng, Yi Offermanns, Stefan Montero, María J. Bustelo, Xosé R. |
author_role |
author |
author2 |
Menacho Márquez, Mauricio Ariel Sevilla, María A. Albarrán Juárez, Julián Zheng, Yi Offermanns, Stefan Montero, María J. Bustelo, Xosé R. |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Rac1 Vav GTPases Signaling vascular smooth muscle Hypertension Blood pressure Nitric oxide, animal models Nitric oxide Animal models Phosphodiesterase 5 Diabetes |
topic |
Rac1 Vav GTPases Signaling vascular smooth muscle Hypertension Blood pressure Nitric oxide, animal models Nitric oxide Animal models Phosphodiesterase 5 Diabetes |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically engineered mice to manipulate the signaling output of Rac1 in these cells at will using inducible, Cre-loxP-mediated DNA recombination techniques. Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic loss of wild-type Vav2. Conversely, the specific depletion of Rac1 in vSMCs causes defective nitric oxide vasodilation responses and hypertension. Rac1, but not Vav2, also is important for neointima formation but not for hypertension-driven vascular remodeling. These animals also have allowed us to dismiss etiological connections between hypertension and metabolic disease and, most importantly, identify pathophysiological programs that cooperate in the development and consolidation of hypertensive states caused by local vascular tone dysfunctions. Finally, our results suggest that the therapeutic inhibition of Rac1 will be associated with extensive cardiovascular system-related side effects and identify pharmacological avenues to circumvent them. Fil: Fabbiano, Salvatore. Universidad de Salamanca; España Fil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad de Salamanca; España Fil: Sevilla, María A.. Universidad de Salamanca; España Fil: Albarrán Juárez, Julián. Max-planck-instituts Für Herz- Und Lungenforschung; Alemania Fil: Zheng, Yi. Cincinnati Children's Hospital Research Foundation; Estados Unidos Fil: Offermanns, Stefan. Max-planck-instituts Für Herz- Und Lungenforschung; Alemania Fil: Montero, María J.. Universidad de Salamanca; España Fil: Bustelo, Xosé R.. Universidad de Salamanca; España |
description |
Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically engineered mice to manipulate the signaling output of Rac1 in these cells at will using inducible, Cre-loxP-mediated DNA recombination techniques. Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic loss of wild-type Vav2. Conversely, the specific depletion of Rac1 in vSMCs causes defective nitric oxide vasodilation responses and hypertension. Rac1, but not Vav2, also is important for neointima formation but not for hypertension-driven vascular remodeling. These animals also have allowed us to dismiss etiological connections between hypertension and metabolic disease and, most importantly, identify pathophysiological programs that cooperate in the development and consolidation of hypertensive states caused by local vascular tone dysfunctions. Finally, our results suggest that the therapeutic inhibition of Rac1 will be associated with extensive cardiovascular system-related side effects and identify pharmacological avenues to circumvent them. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-10 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/95254 Fabbiano, Salvatore; Menacho Márquez, Mauricio Ariel; Sevilla, María A.; Albarrán Juárez, Julián; Zheng, Yi; et al.; Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells; American Society for Microbiology; Molecular and Cellular Biology; 34; 24; 10-2014; 4404-4419 0270-7306 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/95254 |
identifier_str_mv |
Fabbiano, Salvatore; Menacho Márquez, Mauricio Ariel; Sevilla, María A.; Albarrán Juárez, Julián; Zheng, Yi; et al.; Genetic dissection of the Vav2-Rac1 signaling axis in vascular smooth muscle cells; American Society for Microbiology; Molecular and Cellular Biology; 34; 24; 10-2014; 4404-4419 0270-7306 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/MCB.01066-14 info:eu-repo/semantics/altIdentifier/doi/10.1128/MCB.01066-14 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Society for Microbiology |
publisher.none.fl_str_mv |
American Society for Microbiology |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613907593822208 |
score |
13.070432 |