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Objective Vasa vasorum neovascularization is a key feature of atherosclerosis and strongly associated with inflammatory infiltrate, 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 healthy male Ba-Ma mini pigs were randomly divided into three groups, six pigs in each group.The pigs in the normal (N) group were feed on normal diet for 18 weeks without balloon injury surgery.The pigs in the atherosclerotic control (AS) group and AS+Endostar group were feed on high-cholesterol diet after balloon injury surgery for 12 weeks then treatment with PBS or Endostar for additional 6 weeks on the high-cholesterol diet.After the treatment, body weight and plasma concentrations of lipid and serum inflammatory markers hs-CRP and IL-6 were measured.The abdominal aortas where injured by balloon catheter were taken for pathological assay and western blot analysis.The intima-media thickness were measured by hematoxylin and eosin (HE) staining, the number of vasa vasorum was measured by immunohistochemistry via monoclonal antibody vWF staining, and the expression of β-catenin and VEGF were measured by western blot and immunohistochemistry via monoclonal antibody β-catenin and VEGF staining.Fesults Body weight and plasma concentrations of lipid were significant higher in the AS group compared with N group (p<0.05), attesting to the success of the high-cholesterol diet feeding, however, no statistical differences were noted between AS group and AS+Endostar group.Serunm inflammatory markers hs-CRP and IL-6 levels showed no significant difference among three groups indicating early atherosclerosis in this swine model was not accompanied by a change in serum inflammatory markers.Histopathology revealed foam cell accumulation and increased vasa vasorum density/intima-media thickness (IMT) in AS group (AS group vs N group, p<0.05), and the Endostar treatment significantly alleviated atherosclerosis with decreased vasa vasorum density and IMT (p<0.05, AS vs AS+Endostar).Western blot analysis revealed that the expression of angiogenesis markers VEGF and β-catenin in the atherosclerotic abdominal aortic wall was significantly reduced by Endostar treatment.In addition, immunohistochemistry results showed VEGF and β-catenin was predominately localized in endothelial cells of adventitial vasa vasorum in the abdominal aortic wall.Conclusion This study support the role of vasa vasorum neovascularization in the development of atherosclerosis and a therapeutic potential of anti-angiogenesis intervention in atherosclerosis.