Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway

Autores
Cidad, Pilar; Velado, Eduardo Miguel; Ruiz McDavitt, Christian; Alonso, Esperanza; Jiménez Pérez, Laura; Asuaje, Agustín; Carmona Viglianco, Yamila Virginia; García Arribas, Daniel; López, Javier; Marroquín, Yngrid; Fernández, Mirella; Roqué, Mercè; Pérez García, M. Teresa; López López, José Ramón
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.
Fil: Cidad, Pilar. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Velado, Eduardo Miguel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Ruiz McDavitt, Christian. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Alonso, Esperanza. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Jiménez Pérez, Laura. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Asuaje, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Carmona Viglianco, Yamila Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: García Arribas, Daniel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: López, Javier. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; España
Fil: Marroquín, Yngrid. Hospital Clínico Universitario. Servicio de Nefrología; España
Fil: Fernández, Mirella. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; España
Fil: Roqué, Mercè. Universidad de Barcelona; España
Fil: Pérez García, M. Teresa. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: López López, José Ramón. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Materia
Cell Signaling
Kv1.3 Channels
Phenotypic Switch
Vascular Remodeling
Vascular Smooth Muscle Cell Proliferation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79195
Acceder
id CONICETDig_5db7c7eb153813194b35c21b3bf2d416
oai_identifier_str oai:ri.conicet.gov.ar:11336/79195
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathwayCidad, PilarVelado, Eduardo MiguelRuiz McDavitt, ChristianAlonso, EsperanzaJiménez Pérez, LauraAsuaje, AgustínCarmona Viglianco, Yamila VirginiaGarcía Arribas, DanielLópez, JavierMarroquín, YngridFernández, MirellaRoqué, MercèPérez García, M. TeresaLópez López, José RamónCell SignalingKv1.3 ChannelsPhenotypic SwitchVascular RemodelingVascular Smooth Muscle Cell ProliferationPhenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.Fil: Cidad, Pilar. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Velado, Eduardo Miguel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Ruiz McDavitt, Christian. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Alonso, Esperanza. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Jiménez Pérez, Laura. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Asuaje, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Carmona Viglianco, Yamila Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: García Arribas, Daniel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: López, Javier. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; EspañaFil: Marroquín, Yngrid. Hospital Clínico Universitario. Servicio de Nefrología; EspañaFil: Fernández, Mirella. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; EspañaFil: Roqué, Mercè. Universidad de Barcelona; EspañaFil: Pérez García, M. Teresa. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: López López, José Ramón. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; EspañaSpringer2015-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79195Cidad, Pilar; Velado, Eduardo Miguel; Ruiz McDavitt, Christian; Alonso, Esperanza; Jiménez Pérez, Laura; et al.; Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway; Springer; Pflugers Archiv-European Journal of Physiology; 467; 8; 8-2015; 1711-17220031-67681432-2013CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-014-1607-yinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00424-014-1607-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:31Zoai:ri.conicet.gov.ar:11336/79195instacron: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:34982025-09-03 09:57:32.226CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
title Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
spellingShingle Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
Cidad, Pilar
Cell Signaling
Kv1.3 Channels
Phenotypic Switch
Vascular Remodeling
Vascular Smooth Muscle Cell Proliferation
title_short Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
title_full Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
title_fullStr Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
title_full_unstemmed Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
title_sort Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
dc.creator.none.fl_str_mv Cidad, Pilar
Velado, Eduardo Miguel
Ruiz McDavitt, Christian
Alonso, Esperanza
Jiménez Pérez, Laura
Asuaje, Agustín
Carmona Viglianco, Yamila Virginia
García Arribas, Daniel
López, Javier
Marroquín, Yngrid
Fernández, Mirella
Roqué, Mercè
Pérez García, M. Teresa
López López, José Ramón
author Cidad, Pilar
author_facet Cidad, Pilar
Velado, Eduardo Miguel
Ruiz McDavitt, Christian
Alonso, Esperanza
Jiménez Pérez, Laura
Asuaje, Agustín
Carmona Viglianco, Yamila Virginia
García Arribas, Daniel
López, Javier
Marroquín, Yngrid
Fernández, Mirella
Roqué, Mercè
Pérez García, M. Teresa
López López, José Ramón
author_role author
author2 Velado, Eduardo Miguel
Ruiz McDavitt, Christian
Alonso, Esperanza
Jiménez Pérez, Laura
Asuaje, Agustín
Carmona Viglianco, Yamila Virginia
García Arribas, Daniel
López, Javier
Marroquín, Yngrid
Fernández, Mirella
Roqué, Mercè
Pérez García, M. Teresa
López López, José Ramón
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cell Signaling
Kv1.3 Channels
Phenotypic Switch
Vascular Remodeling
Vascular Smooth Muscle Cell Proliferation
topic Cell Signaling
Kv1.3 Channels
Phenotypic Switch
Vascular Remodeling
Vascular Smooth Muscle Cell Proliferation
dc.description.none.fl_txt_mv Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.
Fil: Cidad, Pilar. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Velado, Eduardo Miguel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Ruiz McDavitt, Christian. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Alonso, Esperanza. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Jiménez Pérez, Laura. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Asuaje, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: Carmona Viglianco, Yamila Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: García Arribas, Daniel. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: López, Javier. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; España
Fil: Marroquín, Yngrid. Hospital Clínico Universitario. Servicio de Nefrología; España
Fil: Fernández, Mirella. Hospital Clínico Universitario. Servicio de Cardiología y Cirugía Cardíaca; España
Fil: Roqué, Mercè. Universidad de Barcelona; España
Fil: Pérez García, M. Teresa. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
Fil: López López, José Ramón. Universidad de Valladolid; España. Consejo Superior de Investigaciones Científicas; España
description Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
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/11336/79195
Cidad, Pilar; Velado, Eduardo Miguel; Ruiz McDavitt, Christian; Alonso, Esperanza; Jiménez Pérez, Laura; et al.; Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway; Springer; Pflugers Archiv-European Journal of Physiology; 467; 8; 8-2015; 1711-1722
0031-6768
1432-2013
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79195
identifier_str_mv Cidad, Pilar; Velado, Eduardo Miguel; Ruiz McDavitt, Christian; Alonso, Esperanza; Jiménez Pérez, Laura; et al.; Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway; Springer; Pflugers Archiv-European Journal of Physiology; 467; 8; 8-2015; 1711-1722
0031-6768
1432-2013
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00424-014-1607-y
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
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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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score 13.13397

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