31 páginas, 6 figuras, adicionales 6 figuras y 3 tablas.[Objective]: Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability to switch to a noncontractile, migratory, and proliferating phenotype. Although the participation of ion channels in this phenotypic modulation (PM) has been described previously, changes in their expression are poorly defined because of their large molecular diversity. We obtained a global portrait of ion channel expression in contractile versus proliferating mouse femoral artery VSMCs, and explored the functional contribution to the PM of the most relevant changes that we observed.
[Methods and Results]: High-throughput real-time polymerase chain reaction of 87 ion channel genes was performed in 2 experimental paradigms: an in vivo model of endoluminal lesion and an in vitro model of cultured VSMCs obtained from explants. mRNA expression changes showed a good correlation between the 2 proliferative models, with only 2 genes, Kv1.3 and Kvβ2, increasing their expression on proliferation. The functional characterization demonstrates that Kv1.3 currents increased in proliferating VSMC and that their selective blockade inhibits migration and proliferation.
[Conclusion]: These findings establish the involvement of Kv1.3 channels in the PM of VSMCs, providing a new therapeutical target for the treatment of intimal hyperplasia.This work was supported by Ministerio de Sanidad, Instituto de
Salud Carlos III grants R006/009 (Red Heracles), FS041139-0
(M.R.), and PI041044 (J.R.L.-L.); Ministerio de Educacio´n y
Ciencia grants BFU2004-05551 (M.T.P.-G.) and BFU2007-61524
(J.R.L.-L.); and Junta de Castilla y Leon grant GR242. Dr
Moreno-Domínguez is a fellow of the Spanish Ministerio de
Educacion y Ciencia.Peer reviewe
