title: Dose-dependent neovascularization-promoting effect of adenovirus vector CI-1023 in a rat hindlimb ischaemic model.
abstract: CI-1023 (AdGVVEGF121.10) is a replication-deficient adenovirus vector (complete E1a-, partial E1b-, partial E3-) delivering human vascular endothelial growth factor-121 gene. Previous studies from this group have established that CI-1023 can successfully transfer human vascular endothelial growth factor-121 gene resulting in local tissue expression of vascular endothelial growth factor protein. The purpose of this study was to evaluate neovascularization-promoting potency and efficacy of CI-1023 in a wide dose range. In a rat hindlimb ischaemic model, we measured neovascularization-promoting effect of CI-1023 using three end-points: post mortem angiography, immuno-histochemistry and Laser Doppler scanning of tissue blood perfusion. Neovascularization-promoting activity of CI-1023 over the dose range of 4 x 10(6) pu-4 x 10(10) pu was evaluated. Our data demonstrated an obvious dose-dependent effect between 4 x 10(6) pu-4 x 10(8) pu. The neovascularizing effect is somewhat plateaued at the levels between 4 x 10(8) pu and 4 x 10(10) pu. We conclude CI-1023 is a potent neovascularization-promoting compound, with a dose-dependent effect between 4 x 10(6) pu-4 x 10(8) pu in the rat hindlimb ischaemic model.
authors.affiliation: Human Biomarker Center, TM&T, GlaxoSmithKline, Philadelphia, PA 19104, USA. he.4.wang@gsk.com
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Joan A
authors.initials: JA
authors.lastname: Keiser
authors.forename: Bronia
authors.initials: B
authors.lastname: Olszewski
authors.forename: David
authors.initials: D
authors.lastname: Brammer
authors.forename: David
authors.initials: D
authors.lastname: Gordon
mesh_terms: D042501:Angiogenic Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000792:Angiography / Q000379:methods; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects*; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C437806:AdGVVEGF121.10; D042501:Angiogenic Proteins; D008222:Lymphokines; D042442:Vascular Endothelial Growth Factors