Calcineurin-NFAT pathway mediates phenylephrine-induced vascular smooth muscle cell proliferation
- VernacularTitle:CaN-NFAT信号通路参与苯肾上腺素介导的血管平滑肌细胞增殖
- Author:
Xiao PANG
;
Peiying HE
;
Ningling SUN
- Publication Type:Journal Article
- Keywords:
phenylephrine;
calcineurin;
nuclear factor of activated T cells;
proliferation;
vascular smooth muscle cells
- From:
Basic & Clinical Medicine
2006;0(10):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective Calcineurin-NFAT pathway in the regulation of VSMCs proliferation induced by catecholamines.Methods Primary VSMCs from rat aorta were used as the experimental model.Proliferation of VSMCs was measured by MTT assay and cell count.Calcineurin protein and its activity were assayed with immunoblotting and free inorganic phosphate content analysis respectively.Localization of NFATc1 was detected by immunofluorescence staining.Results Phenylephrine(PE,an ?1-adrenoceptor agonist) increased VSMCs proliferation.Prazosin(an ?1-adrenoceptor antagonist),cyclosporin A(CsA,an inhibitor of calcineurin) and chelerythrine(an inhibitor of PKC) decreased PE-induced absorbance and cell number.Timolol(?-adrenoceptor antagonist) has no effect on absorbance and cell number induced by PE.Additional treatment with CsA further inhibited PE-induced absorbance and cell number compared with the chelerythrine pretreatment group.CsA and chelerythrine alone had no significant effect on either absorbance or cell number.CsA decresed PE-induced alcineurin level and its activity.NFATc1 was translocated from cytoplasm to nucleus upon treatment with PE.This translocation was reversed by CsA.Conclusion CsA partially inhibits PE-induced VSMCs proliferation via inhibiting calcineurin activity and NFATc1 nuclear translocation.Calcineurin-NFATc1 pathway is involved in hyperplastic growth of VSMCs induced by catecholamines.
