RT info:eu-repo/semantics/article
T1 K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation
A1 Cidad Velasco, María del Pilar
A1 Novensá, Laura
A1 Garabito, M.
A1 Batlle, M.
A1 Dantas, A. P.
A1 Heras i Fortuny, Maria Magdalena
A1 López López, José Ramón
A1 Pérez García, María Teresa
A1 Roqué, Mercé
K1 Potassium channels
K1 Canales de potasio
K1 Intimal hyperplasia
K1 Hiperplasia intimal
K1 Hypertension
K1 Hipertensión
AB K+ channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. Purpose: To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion . Methods: Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K+ channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro. Results: Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84±4 % vs. 70±5 % in BPN, p<0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18± 6 % vs. 58±20 % with vehicle, p<0.05). Conclusions: Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.
PB Springer Link
SN 1573-7241
YR 2014
FD 2014
LK http://uvadoc.uva.es/handle/10324/44591
UL http://uvadoc.uva.es/handle/10324/44591
LA eng
NO Cardiovascular Drugs and Therapy, 2014, vol. 28. p. 501-511
NO Producción Científica
DS UVaDOC
RD 17-jul-2024