The Overexpression Of 12-lipoxygenase Attenuate The Improvement Of Atorvastatin On Endthelial Function

Objective To investigate the effects of 12-lipoxygenase(12-LO) on endothelial function improved by atorvastatin.Methods Sprague Dawley rats were randomly divided into sham group, balloon injury group(BI), balloon injury+Atorvastatin(BI+Ator) group, balloon injury+Atorvastatin+Lentivirus-GFP group(BI+Ator+Lv-GFP), balloon injury+Atorvastatin+Lentivirus-12-LO group(BI+ Ator+Lv-12-LO). Except the sham group, all the rats were received the carotid artery balloon injury operation. BI+Ator+Lv-GFP group and BI+Ator+Lv-12-LO group were followed by transfected lentivirus expressing GFP or 12-LO into injuried artery. Pharmacological intervention groups were given atorvastatin(10mg/kg/d) for 14 days. The transfection efficiency of lentivirus was detected by fluorescence microscopy and Western blot. Intimal hyperplasia was observed using H&E staining. The expression of endothelial nitric oxide synthase(eNOS), vascular cell adhesion molecule-1(VCAM-1) and intracellular adhesion molecule-1(ICAM-1) were detected by immunohistochemistry and Western blot.Results The pronounced green fluorescence was detected in the neointima of carotid arteries after transfection with Lv-12-LO. And Lv-12-LO up-regulated 12-LO protein expression by Western blot analyses. Compared with sham group, Intima-media thickness(IMT) of BI group was obviously increased. IMT was increased further after transfection with Lv-12-LO. The results of immunohistochemistry and Western blot showed the expression of eNOS in BI group was decreased and the expression of VCAM-1 and ICAM-1 were increased, compared with Sham group. After giving atorvastatin, the expression of eNOS was increased, and the expression of VCAM-1 and ICAM-1 were decreased. Compared with BI+Ator+Lv-GFP group, the expression of eNOS in BI+Ator+Lv-12-LO group was significantly decreased, and the expression of VCAM-1 and ICAM-1 were significantly increased.Conclusion The results demonstrated that overexpression of 12-LO might attenuate the improvement of atorvastatin on endothelial function. The mechanism may be affected the expression of inflammatory factors and endothelial factors.