Abstract:
Objective To investigate the effects of atorvastatin on the expression of protease-activated receptor(PAR)-1in platelet activation and the changes of neointimal hyperplasia after balloon-induced carotid artery injury in cholesterol-fed rabbits. Methods A total of 30 rabbits were randomly treated as follows:control,fed with cholesterol-enriched diet+sham-operated(pure high fat group),fed with cholesterol-enriched diet+balloon-injured(high fat+balloon-injured group),balloon injury and treated with 5mg/(kg·d)atorvastatin(L-atorvastatin group)and10mg/(kg·d)(H-atorvastatin group),n=6. Platelet aggregation rate was measured by turbidimetric platelet aggregometry. The levels of P-selectin and thromboxane B2 were detected by enzyme-linked immunosorbent assay.After 28 days,wall-to-lumen area ratios(W/L)of the injured arteries were calculated using a computer image analysis system and the protein expression of PAR-1in all rabbits was detected with Western blot. HE staining was used to detect carotid morphological changes. Results 1Compared with the pure high fat group,the level of P-selectin,thromboxane B2 and platelet aggregation was significantly increased and reached a peak at 24 th hour after balloon injury. And treatment with atorvastatin dose-dependently decreased the level of P-selectin and thromboxane B2,as well as,inhibited the platelet aggregation(P<0.05).2After high-cholesterol diet and vascular injury,the expression of PAR-1protein significantly increased in comparison with the control group and pure high fat group,whereas it could be markedly decreased by atorvastatin treatment in a dose-dependent manner(pure high fat+balloon-injured group:1.143±0.099 vs control group:0.172±0.028,pure high fat group:0.184±0.035;L-atorvastatin:0.920±0.083,H-atorvastatin:0.091±0.013 vs pure high fat+balloon-injured group:1.143±0.099,all P<0.05).3Compared with control group,the W/L of pure high fat group and pure high fat+balloon-injured group were increased obviously(P<0.05);Treatment with atorvastatin significantly attenuated the neointimal hyperplasia after vascular injury,compared with pure high fat+balloon-injured group,the W/L of L-atorvastatin group and Hatorvastatin group were respectively decreased by 27% and 49%(all P < 0.01). Conclusions Atorvastatin treatment inhibits the expression of PAR-1protein,thromboxane B2 and platelet activation and aggregation,so as to mitigate neointimal hyperplasia after vascular balloon injury in high-cholesterol diet rabbits.