Vascular endothelial grow factor 165 and angiopoitin-1 augment revascularization in a rat hindlimb ischemia model
- VernacularTitle:人血管内皮细胞生长因子-165和人血管生成素-1促进大鼠缺血下肢血管新生
- Author:
Jianrong SONG
;
Zhijian YANG
;
Fumin ZHANG
- Publication Type:Journal Article
- Keywords:
Vascular endothelial growth factor;
Angiopoietin-1;
Angiogenesis;
Gene therapy
- From:
Chinese Journal of Interventional Cardiology
1993;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the angiogenic effects of adenovirus mediated human vascular endothelial growth factor 165 and human angiopoietin-1 (Ad 5-VEGF 165 , Ad 5-Ang-1) in rat models of hindlimb ischemia. Methods Rat models of hindlimb ischemia were established by ligation and peeling off rat′s femoral arteries. Ad-VEGF 165 and Ad-Ang-1 were intramuscularly transferred into the rat ischemic hindlimbs. The expression of VEGF 165 and Ang-1 were examined by Western blotting. Immunohistochemistry was performed to illustrate the effects on rat ischemic muscles after gene transferring. Results (1) Western blotting showed a high expression of VEGF 165 and Ang-1 in the ischemic hindlimb muscle transferred with Ad 5-VEGF 165 and Ad 5-Ang-1 VEGF 165 respectively. (2) There was no significant difference between groups on 7 days after the transfer. The capillary to muscle fiber ratio was significantly higher in the treating groups than that in control groups and were significantly higher in VEGF 165 +Ang-1 group than in VEGF 165 or in Ang-1 groups on day 14th and day 21th. (3) Many structured vessels surrounded by a layer of smooth muscle cells were found in Ad-VEGF 165 and Ad-VEGF 165 +Ad-Ang-1 groups, the number of SMA + vessel per muscle fiber was obviously higher than those in control groups. (4) Enormous cells positive for BrdU appeared in treated muscles in Ang-1, VEGF 165 , VEGF 165 +Ang-1 groups and many of them were positive for C-Kit, an antigen expressed by pluripotent marrow stem cells. Some C-Kit+ cells were incorporated in sites of neovascularization. Conclusion (1) Vascular endothelial growth factor 165 and angiopoietin-1 can promote neovascularization in rat models of hindlimb ischemia and the angiogenic effect is much more significant in Ad-VEGF+Ad-Ang-1 group. (2) VEGF 165 can increase the number of vessles that are coated with smooth muscle cells which shapes are similar to arterioles. (3) Not only angiogenic effect but perhaps vasculogenic effct also contribute to the neovascularization.