Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study

Producción Científica

Detalles Bibliográficos
Autores: Moreno Estar, Sara, Serrano, Sofía, Arévalo Martínez, Marycarmen, Cidad Velasco, María Del Pilar, López López, José Ramón, Santos García, María Mercedes, Pérez García, María Teresa, Arias Vallejo, Francisco Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Valladolid
Repositorio:UVaDOC. Repositorio Documental de la Universidad de Valladolid
OAI Identifier:oai:uvadoc.uva.es:10324/65357
Acceso en línea:https://doi.org/10.1016/j.actbio.2020.07.053
https://uvadoc.uva.es/handle/10324/65357
Access Level:acceso abierto
Palabra clave:Vascular smooth muscle cells
Intimal hyperplasia
Elastin-like recombinamers
Hydrogels
Kv1.3 channels
Local drug delivery
23 Química
32 Ciencias Médicas
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spelling Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo studyMoreno Estar, SaraSerrano, SofíaArévalo Martínez, MarycarmenCidad Velasco, María Del PilarLópez López, José RamónSantos García, María MercedesPérez García, María TeresaArias Vallejo, Francisco JavierVascular smooth muscle cellsIntimal hyperplasiaElastin-like recombinamersHydrogelsKv1.3 channelsLocal drug delivery23 Química32 Ciencias MédicasProducción CientíficaCoronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previously reported that the inhibition of Kv1.3 channel function with selective blockers represents an effective strategy for the prevention of restenosis in human vessels used for coronary angioplasty procedures. However, delivery systems for controlled release of these drugs have not been investigated. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models. The dose and time course of PAP-1 release from ELRs click hydrogels was able to inhibit human VSMC proliferation in vitro as well as remodeling of human vessels in organ culture and restenosis in in vivo models. We conclude that this combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients. STATEMENT OF SIGNIFICANCE: Vascular surgery strategies for coronary revascularization show a high rate of failure, because of occlusion (restenosis) of the vessel, due to vascular smooth muscle cells proliferation and migration. We have previously reported that blockers of Kv1.3 channels represent an effective anti-restenosis therapy, but delivery systems for their controlled release have not being explored. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models, both in vivo and in vitro, and also in human vessels. We demonstrated that combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients.Unión Europea-Horizonte 2020 (EU H2020-NMP-2014-646075)Ministerio de Economía y Competitividad (BFU2016-75360-R, DTS19/00162, MAT2016-79435-R, MAT2016-78903-R, RTI2018-096320-B-C22)Junta de Castilla y León (VA114P17, VA317P18)Centro en Red de Medicina regenerativa y Terapia celular de Castilla y LeónElsevier2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://doi.org/10.1016/j.actbio.2020.07.053https://uvadoc.uva.es/handle/10324/65357reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://www.sciencedirect.com/science/article/pii/S1742706120304505info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/oai:uvadoc.uva.es:10324/653572026-06-13T12:44:47Z
dc.title.none.fl_str_mv Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
title Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
spellingShingle Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
Moreno Estar, Sara
Vascular smooth muscle cells
Intimal hyperplasia
Elastin-like recombinamers
Hydrogels
Kv1.3 channels
Local drug delivery
23 Química
32 Ciencias Médicas
title_short Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
title_full Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
title_fullStr Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
title_full_unstemmed Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
title_sort Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
dc.creator.none.fl_str_mv Moreno Estar, Sara
Serrano, Sofía
Arévalo Martínez, Marycarmen
Cidad Velasco, María Del Pilar
López López, José Ramón
Santos García, María Mercedes
Pérez García, María Teresa
Arias Vallejo, Francisco Javier
author Moreno Estar, Sara
author_facet Moreno Estar, Sara
Serrano, Sofía
Arévalo Martínez, Marycarmen
Cidad Velasco, María Del Pilar
López López, José Ramón
Santos García, María Mercedes
Pérez García, María Teresa
Arias Vallejo, Francisco Javier
author_role author
author2 Serrano, Sofía
Arévalo Martínez, Marycarmen
Cidad Velasco, María Del Pilar
López López, José Ramón
Santos García, María Mercedes
Pérez García, María Teresa
Arias Vallejo, Francisco Javier
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vascular smooth muscle cells
Intimal hyperplasia
Elastin-like recombinamers
Hydrogels
Kv1.3 channels
Local drug delivery
23 Química
32 Ciencias Médicas
topic Vascular smooth muscle cells
Intimal hyperplasia
Elastin-like recombinamers
Hydrogels
Kv1.3 channels
Local drug delivery
23 Química
32 Ciencias Médicas
description Producción Científica
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.actbio.2020.07.053
https://uvadoc.uva.es/handle/10324/65357
url https://doi.org/10.1016/j.actbio.2020.07.053
https://uvadoc.uva.es/handle/10324/65357
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1742706120304505
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid
instname:Universidad de Valladolid
instname_str Universidad de Valladolid
reponame_str UVaDOC. Repositorio Documental de la Universidad de Valladolid
collection UVaDOC. Repositorio Documental de la Universidad de Valladolid
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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