Effect Of Atorvastatin On Progression Of Experimentally Induced Cerebral Aneurysms In Rats

Background: Endothelial injury is the early pathological changes of cerebral aneurysm(CA)formation.Endothelial progenitor cells(EPC)are critical in preventing or slowing CA formation by by replacing injuried and dysfunctional endothelial cells(ECs).Atorvastatin(ATR),beyond lipid-lowering activity,reportedly promote vascular repair by moblizing endothelial progenitor cells(EPC).We sought to investigate the effect of ATR on vascular degeneration after CA induction in rats.Methods: Adult male Sprague-Dawley rats were induced to form CAs models.They were randomly divided into there groups: control(CTR)group,CA group and CA+ATR treatment group.3 months after CA induction,circulating EPC level,hematological and lipid profiles were measured.Verhoeff-Van Gieson staining was performed to assess pathological change of artery wall.RT-PCR was also performed to evaluate the expression of inflammation-related genes in aneurysmal wall including nuclear factor k B(NF-k B),inducible nitric oxide synthase(i NOS),endothelial nitric oxide synthase(e NOS),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9).Results: Circulating EPCs were significantly lower in CA group as compared to CTR group.ATR significantly restored the impaired level of circulating EPC without changing hematological and lipid profiles 3 months after CA induction.ATR markedly inhibitted endothelial injury,media thinning and CA enlargement,which was accompanied by reducing vascular inflammation of NF-k B,i NOS,MMP-2,MMP-9.As for e NOS,it is reduced in CA group,while ATR could increase the level of e NOS.Conclusions: Our preliminary results demonstrated that the mobilization of EPC and improvement of endothelial function by ATR may contribute to the prevention of anueyrsmal degeneration.