Aim: Vasa vasorum neovascularization is a key feature of atherosclerosis and is strongly associated with inflammatory infiltration,lipid deposition,intraplaque hemorrhage,and hemosiderin deposit.Here we investigate the effects of Endostar,a strong anti-angiogenic drug,on vasa vasorum neovascularization in the experimental porcine model of early atherosclerosis.Methods: Eighteen adult male Ba-Ma mini pigs were randomly divided into three groups,with six animals in each group.The pigs in the normal (N) group were fed a normal diet for 18 weeks without balloon injury surgery.The animals in the atherosclerotic(AS) control group and theAS+Endostar group were fed a hypercholesterolemic diet for 12 weeks after balloon injury surgery,and received either saline or Endostar treatment for an additional six weeks,while remaining on the hypercholesterolemic diet.The atherosclerotic abdominal aorta and levels of serum lipids,TNF-alpha,IL-6and hs-CRP were analyzed at 18 weeks.Results: The AS group had significantly higher body weight and serum lipid concentration levels than the N group (p<0.05),attesting to the success of the hypercholesterolemic diet.However,no statistical differences were noted between the AS and AS+Endostar groups.Histopathology results revealedthat vasa vasorum density and intima-media thickness (IMT) had also increased in the AS group,as compared with the N group (p<0.05).Endostar treatment significantly alleviated atherosclerosis with decreased vasa vasorum density and IMT (AS vs.AS+Endostar,p<0.05).The results from western blot analysis indicated that the expression of VEGF,β-catenin and TNF-alpha in the atherosclerotic abdominal aorta was considerably reduced by the Endostar treatment.In addition,immunohistochemistry results showed that the angiogenesis markers VEGF and β-catenin were predominately localized in endothelial cells of adventitial vasa vasorum.The levels of serum inflammatory markers TNF-alpha,hs-CRPandIL-6 were significantly higher in the AS groupcompared with the N group (p<0.05),but showed no significant difference during the Endostar treatment,suggesting thatlocalinhibition of angiogenesis was not accompaniedby a change in serum inflammatory markers and the inhibitive effect of Endostar onlocal TNF-alpha expressionmay be due tothe prevention of vasavasorum neovascularization.Conclusions: Our results demonstrated that Endostar treatment inhibitedvasa vasorum neovascularization and AS progression in the experimental porcine model of early atherosclerosis,thus supports the role of vasa vasorum neovascularization in the development of atherosclerosis and the therapeutic potential of anti-angiogenesis intervention in atherosclerosis.