@article{APS5142,
author = {Xiao Pang and Ning-ling Sun},
title = {Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation},
journal = {Acta Pharmacologica Sinica},
volume = {30},
number = {5},
year = {2016},
keywords = {},
abstract = {Aim: Catecholamine-induced vascular smooth muscle cell (VSMC) proliferation is one of the major events in the pathogenesis of atherosclerosis and vascular remodeling. The calcineurin-NFAT pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the calcineurin-NFAT pathway was involved in the regulation of phenylephrine-induced VSMC proliferation.
Methods: Proliferation of VSMC was measured using an MTT assay and cell counts. Localization of NFATc1 was detected by immunofluorescence staining. NFATc1-DNA binding was determined by EMSA and luciferase activity analyses. NFATc1 and calcineurin levels were assayed by immunoprecipitation.
Results: Phenylephrine (PE, an α1-adrenoceptor agonist) increased VSMC proliferation and cell number. Prazosin (an α1-adrenoceptor antagonist), cyclosporin A (CsA, an inhibitor of calcineurin) and chelerythrine (an inhibitor of PKC) decreased PE-induced proliferation and cell number. Additional treatment of VSMC with CsA or chelerythrine further inhibited proliferation and cell number in the chelerythrine-pretreatment group and the CsA-pretreatment group. CsA and chelerythrine alone had no effect on either absorbance or cell number. CsA decreased PE-induced calcineurin levels and activity. NFATc1 was translocated from the cytoplasm to the nucleus upon treatment with PE. This translocation was reversed by CsA. CsA decreased the PE-induced NFATc1 level in the nucleus. PE increased NFAT's DNA binding activity and NFAT-dependent reporter gene expression. CsA blocked these effects.
Conclusion: CsA partially suppresses PE-induced VSMC proliferation by inhibiting calcineurin activity and NFATc1 nuclear translocation. The calcineurin-NFATc1 pathway is involved in the hyperplastic growth of VSMC induced by phenylephrine.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/5142}
}