RT info:eu-repo/semantics/article
T1 Kv1.3 blockade inhibits proliferation of vascular smooth muscle cells in vitro and intimal hyperplasia in vivo
A1 Bobi, Joaquim
A1 Garabito, Manel
A1 Solanes, Nuria
A1 Cidad Velasco, María Del Pilar
A1 Ramos-Pérez, Víctor
A1 Ponce, Alberto
A1 Rigol, Montserrat
A1 Freixa, Xavier
A1 Pérez-Martínez, Claudia
A1 Pérez de Prado, Armando
A1 Fernández-Vázquez, Felipe
A1 Sabaté, Manel
A1 Borrós, Salvador
A1 López López, José Ramón
A1 Pérez García, María Teresa
A1 Roqué, Mercé
AB 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.
SN 1931-5244
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/65369
UL https://uvadoc.uva.es/handle/10324/65369
LA spa
NO Transl Res . 2020 Oct:224:40-54. doi: 10.1016/j.trsl.2020.06.002. Epub 2020 Jun 6.
DS UVaDOC
RD 22-dic-2024