RT info:eu-repo/semantics/article
T1 Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
A1 Moreno Estar, Sara
A1 Serrano, Sofía
A1 Arévalo Martínez, Marycarmen
A1 Cidad Velasco, María Del Pilar
A1 López López, José Ramón
A1 Santos García, María Mercedes
A1 Pérez García, María Teresa
A1 Arias Vallejo, Francisco Javier
AB 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.
SN 1742-7061
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/65357
UL https://uvadoc.uva.es/handle/10324/65357
LA spa
NO Acta Biomater . 2020 Oct 1:115:264-274. doi: 10.1016/j.actbio.2020.07.053. Epub 2020 Aug 6.
DS UVaDOC
RD 21-dic-2024