Artículo
Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway
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
Fecha de publicación:
08/2015
Editorial:
Springer
Revista:
Pflugers Archiv-European Journal of Physiology
ISSN:
0031-6768
e-ISSN:
1432-2013
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Resumen
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.
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Identificadores
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(CENEXA)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Citación
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
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