論文 - 詳細
| RRC ID | 32582 |
|---|---|
| 著者 | Yamauchi A, Ito Y, Morikawa M, Kobune M, Huang J, Sasaki K, Takahashi K, Nakamura K, Dehari H, Niitsu Y, Abe T, Hamada H. |
| タイトル | Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model. |
| ジャーナル | J Gene Med |
| Abstract |
BACKGROUND:Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) play important roles in vascular formation and maturation, suggesting that the combination of these two would be a promising therapy for ischemia. However, it remains unclear what the best schedule of administration of these cytokines might be. METHODS:Six experimental groups were used to prepare the rabbit ischemic hindlimb model following naked plasmid intramuscular administration as follows: empty vector (C), single gene (Ang1, A; VEGF, V), Ang-1 followed by VEGF (A - V), co-administration of Ang1 and VEGF (A + V), and VEGF followed by Ang1 (V - A). RESULTS:Thirty days after gene administration, A - V showed a significantly increased blood pressure and blood-flow recovery in the ischemic limb compared with the control group. Histological findings by alpha-smooth muscle-actin (alpha-SMA) staining revealed that the two combination groups had more mature vessels as compared with the control group. Significantly, A - V revealed the highest density of alpha-SMA-positive vessels compared with VEGF alone or Ang1 alone. Angiographic assessment revealed that A - V had a greater increased arterial diameter compared with VEGF alone. Edema, one of the major adverse effects induced by VEGF, was not found in A - V throughout the experiments, while VEGF alone and V - A showed severe edema induced by VEGF. CONCLUSIONS:The pre-administration of Ang1 followed by VEGF resulted in an improvement of hemodynamic status, an increased number of vessels covered with alpha-actin-positive mural cells, and prevention of VEGF-mediated edema. Thus, priming by Ang1 gene administration would be beneficial for therapeutic angiogenesis in VEGF gene therapy. |
| 巻・号 | 5(11) |
| ページ | 994-1004 |
| 公開日 | 2003-11-1 |
| DOI | 10.1002/jgm.439 |
| PMID | 14601137 |
| MeSH | Angiography Angiopoietin-1 / genetics Angiopoietin-1 / therapeutic use* Animals Blood Pressure DNA Primers Disease Models, Animal Gene Expression* Genetic Therapy* Humans Ischemia / drug therapy* Male Microspheres Muscle, Skeletal / metabolism Neovascularization, Physiologic / genetics* Plasmids / genetics Rabbits Scrotum / drug effects Scrotum / physiology Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / therapeutic use* |
| IF | 3.258 |
| 引用数 | 54 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| リソース情報 | |
| 遺伝子材料 | pCAhAng1 (RDB03963) pDisplayhAng1 (RDB03987) pRxhVEGFbsr (RDB03986). |