• Pilar Cidad, Alejandro Moreno-Domínguez, Laura Novensá, Mercé Roqué, Leire Barquín, Magda Heras, M Teresa Pérez-García, and José R López-López.
• Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo superior de Investigaciones Cientificas, Valladolid, Spain.
• Arterioscler. Thromb. Vasc. Biol. 2010 Jun 1; 30 (6): 1203-11.

ObjectiveVascular 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 ResultsHigh-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 Kvbeta2, 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.ConclusionsThese findings establish the involvement of Kv1.3 channels in the PM of VSMCs, providing a new therapeutical target for the treatment of intimal hyperplasia.

42 keywords...

hide…