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oai:uvadoc.uva.es:10324/653572025-02-04T08:17:36Zcom_10324_22821com_10324_954com_10324_894com_10324_43677col_10324_22822col_10324_43678

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 2024-01-30T13:49:09Z 2024-01-30T13:49:09Z 2020 Acta Biomaterialia, octubre 2020, vol. 115, p. 264-274. 1742-7061 https://uvadoc.uva.es/handle/10324/65357 10.1016/j.actbio.2020.07.053 264 274 Acta Biomaterialia 115 Producción Científica Coronary 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 León application/pdf eng Elsevier info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/4.0/ © 2020 Acta Materialia Inc Atribución-NoComercial-SinDerivados 4.0 Internacional Vascular smooth muscle cells Intimal hyperplasia Elastin-like recombinamers Hydrogels Kv1.3 channels Local drug delivery 23 Química 32 Ciencias Médicas Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion https://www.sciencedirect.com/science/article/pii/S1742706120304505 SI