Synergistic Effect of Human Vascular Endothelial Grow Factor 165 and Angiopoietin-1 Augment Revascularization in Rat Models of Hindlimb Ischemia

Document Type

Article

Publication Date

7-1-2004

Description

Aim: To study the angiogenic effects of adenovirus-mediated human vascular endothelial growth factor 165(Ad-VEGF165) and human angiopoietin-1 (Ad-Ang1) gene on ischemia hindlimb of rat models. Methods: Totally 84 male SD rats were divided into 7 groups of 12 rats in each group: normal group, sham operation group, ligation group, green fluorescence protein (GFP) group (as the virus control group), Ang1 group, VEGF165 group, and Ang1 + VEGF165 group. Rat models of hindlimb ischemia were induced by ligation, Ad-VEGF165 and Ad-Ang1 were intramuscularly injected into the rat ischemic hindlimb. The expression of VEGF165 and Ang1 were examined by Western blotting. Immunohistochemistry was performed to illustrate the effects on rat ischemic muscles after gene transferring. Results: 1 High expressions of human VEGF165 and Ang1 were observed after injection of Ad-VEGF165 and Ad-Ang1. 2 There was no significant difference in the number of new blood capillaries between the treatment groups and the control group 7 days after transfection, while 14 and 21 days after transfection, the number of blood capillary/skeletal muscle fiber in the Ang1 and VEGF165 groups was significantly higher than those in the control group (F = 24.53, P < 0.01), and that in the VEGF165 + Ang1 group were obviously higher than that in the VEGF165 or Ang1 group (F = 12.22, P < 0.01). 3 Many structured vessels surrounded by a layer of smooth muscle cells alpha (α-SMA) were found in the VEGF165 group and VEGF165 + Ang1 group, and the ratio of SMA + number to muscle fiber was obviously higher than that in the control group (F = 9.73, P < 0.01). 4 Enormous BrdU positive cell infiltration appeared in the muscles in the Ang1, VEGF165 and VEGF165 + Ang1 groups, and many of them were positive for C-Kit, and positive labeling of C-Kit was also observed in the new vascular endothelial cells (F = 9.73 - 35.10, P < 0.01). Conclusion: 1 VEGF165 and Ang1 can promote the neovascularization in rat model of hindlimb ischemia and the angiogenic effect is more significant in the VEGF165 + Ang1 group. 2 VEGF165 can increase the number of vessels which are coated with SMC and seemed to be arterioles. 3 Not only angiogenic effect but perhaps vasculogenic effect also contributes to the neovascularization.

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