RRC ID 32582
Author Yamauchi A, Ito Y, Morikawa M, Kobune M, Huang J, Sasaki K, Takahashi K, Nakamura K, Dehari H, Niitsu Y, Abe T, Hamada H.
Title Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model.
Journal 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.
Volume 5(11)
Pages 994-1004
Published 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 1.561
Times Cited 54
DNA material pCAhAng1 (RDB03963) pDisplayhAng1 (RDB03987) pRxhVEGFbsr (RDB03986).