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    • SCIENTIFIC PRODUCTION
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    • Edición Génica para el Estudio de Canales Iónicos Vasculares y Proteínas Mitocondriales (VASCUMIT)
    • VASCUMIT - Artículos de revista
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    Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/65369

    Título
    Kv1.3 blockade inhibits proliferation of vascular smooth muscle cells in vitro and intimal hyperplasia in vivo
    Autor
    Bobi, Joaquim
    Garabito, Manel
    Solanes, Nuria
    Cidad Velasco, María Del PilarAutoridad UVA Orcid
    Ramos-Pérez, Víctor
    Ponce, Alberto
    Rigol, Montserrat
    Freixa, Xavier
    Pérez-Martínez, Claudia
    Pérez de Prado, Armando
    Fernández-Vázquez, Felipe
    Sabaté, Manel
    Borrós, Salvador
    López López, José RamónAutoridad UVA Orcid
    Pérez García, María TeresaAutoridad UVA Orcid
    Roqué, Mercé
    Año del Documento
    2020
    Documento Fuente
    Transl Res . 2020 Oct:224:40-54. doi: 10.1016/j.trsl.2020.06.002. Epub 2020 Jun 6.
    Abstract
    The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in 2 porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. The therapeutic potential of PAP-1 was then evaluated in vivo in swine models of ISR and AV. At 15-days follow-up, morphometric analysis demonstrated a substantial reduction of luminal stenosis in the allografts treated with PAP-1 (autograft 2.72 ± 1.79 vs allograft 10.32 ± 1.92 vs allograft + polymer 13.54 ± 8.59 vs allograft + polymer + PAP-1 3.06 ± 1.08 % of luminal stenosis; P = 0.006) in the swine model of femoral artery transplant. In the pig model of coronary ISR, using a prototype of PAP-1-eluting stent, no differences were observed regarding % of stenosis compared to control stents (31 ± 13 % vs 37 ± 18%, respectively; P = 0.372) at 28-days follow-up. PAP-1 treatment was safe and did not impair vascular healing in terms of delayed endothelialization, inflammation or thrombosis. However, an incomplete release of PAP-1 from stents was documented. We conclude that the use of selective Kv1.3 blockers represents a promising therapeutic approach for the prevention of intimal hyperplasia in AV, although further studies to improve their delivery method are needed to elucidate its potential in ISR.
    ISSN
    1931-5244
    Revisión por pares
    SI
    DOI
    10.1016/j.trsl.2020.06.002
    Version del Editor
    https://doi.org/10.1016/j.trsl.2020.06.002
    Idioma
    spa
    URI
    https://uvadoc.uva.es/handle/10324/65369
    Tipo de versión
    info:eu-repo/semantics/acceptedVersion
    Derechos
    openAccess
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    • VASCUMIT - Artículos de revista [47]
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