|Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation|
|Pang, Xiao1,2; Sun, Ning-ling1|
|关键词||Phenylephrine Calcineurin Nuclear Factor Of Activated t Cells Proliferation Vascular Smooth Muscle Cells|
|刊名||ACTA PHARMACOLOGICA SINICA|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||ACTIVATED T-CELLS ; RECEPTOR TYROSINE KINASE ; NUCLEAR FACTOR ; NEOINTIMA FORMATION ; CYCLOSPORINE-A ; CAROTID-ARTERY ; DNA-SYNTHESIS ; GROWTH-FACTOR ; RAT ; TRANSCRIPTION|
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 alpha(1)-adrenoceptor agonist) increased VSMC proliferation and cell number. Prazosin (an alpha(1)-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.
|作者单位||1.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100044, Peoples R China|
2.Xinjiang Shihezi Univ, Affiliated Hosp 1, Dept Geratol, Coll Med, Xinjiang 832008, Peoples R China
|Pang, Xiao,Sun, Ning-ling. Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation[J]. ACTA PHARMACOLOGICA SINICA,2009,30(5):537-544.|
|APA||Pang, Xiao,&Sun, Ning-ling.(2009).Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation.ACTA PHARMACOLOGICA SINICA,30(5),537-544.|
|MLA||Pang, Xiao,et al."Calcineurin-NFAT signaling is involved in phenylephrine-induced vascular smooth muscle cell proliferation".ACTA PHARMACOLOGICA SINICA 30.5(2009):537-544.|