Study Of Nucluar Receptor Nur77 Regulated Vascular Smooth Muscle Cells Proliferation

Objective:To study the mechanism of restenosis for the prevention and treatment by PTA(percutaneous transcather angioplasty)through establishing an model.Methods:Under median cervical incision, to eploreou mouse carotid artery and then clip the segments of ICA at the origination and CCA near the cardiac side of bifucation, balloon catheter with guided wire were finally inserted from proximal cardiac side of the ligated EC A to perform TA after withdrawing the clipper. Histological and morphological analys-is with the control of normal left CCA were carried out during different follow up periods. And we investigated the effects of atorvastatin on the modle.Results:Histopathological and morphometric analysis indicating thro-mlmsis was the main changes in early stage and followed by VSMC from media to intima and irregular proliferation leading to obviously intimal thicking and restenosis.Atorvastatin decended the media thickness and area ratios (P<0.05)Conclusions:This experimental study show low mortality, high pra-cticability and good reproducibility of the model as an ideal presentation for study the mechanism and the prevention of restenosis.Objective:To investigate the effects of atorvastatin on the expression of Nur77 which is overexpressed in arteriosclerosis lesion and has pro- or anti-proliferative effects on vascular smooth muscle cells (VSMCs).Methods:By using rat carotid artery postangioplasty restenosis models, we investigated the effects of atorvastatin on the expression of Nur77 by immunohistochemistry, RT-PCR, and Western blot.Results:Nur77 was up-regulated in neointima, but down-regulated by atorvastatin in rat carotid artery postangioplasty restenosis models.Conclusions:Down-regulation of Nur77 by atorvastatin suggests a novel therapy strategy for atherogenesis based on suppression of VSMCs proliferation.Objective:To investigate the expression of PDGF-induced Nur77 mechanism and relationship with proliferation of vascular smooth muscle cells.Methods:Isolated and cultured VSMC.The expression of Nur77,ERK, PCNA induced by PDGF were checked after incubation with PD98059, atorvastatin, Nur77siRNA respectively.Results:PDGF-B induced the expression of Nur77 in VSMC through ERK-MAPK signaling pathway.Atorvastatin effected the PDGF-induced Nur77 expression. VSMC proliferation is attenuated in Nur77-deficient cells.Conclusions:Nur77 regulated VSMC proliferation induced by PDGF. Atorvastatin enduced VSMC proliferation by effecting the expression of Nur77.This may be a new mechanism by which statins affected NF-kB activity by regulating the Nur77 expression.Down-regulation of Nur77 suggests a novel therapy strategy for atherogenesis based on suppression of VSMC proliferation.