title: Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.
abstract: BACKGROUND
  We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo.
  
  
  RESULTS
  Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury.
  
  
  CONCLUSIONS
  Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.
authors.affiliation: Experimental Physiology and Pharmacology Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1650, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Lazarous
authors.forename: M
authors.initials: M
authors.lastname: Shou
authors.forename: M
authors.initials: M
authors.lastname: Scheinowitz
authors.forename: E
authors.initials: E
authors.lastname: Hodge
authors.forename: V
authors.initials: V
authors.lastname: Thirumurti
authors.forename: A N
authors.initials: AN
authors.lastname: Kitsiou
authors.forename: J A
authors.initials: JA
authors.lastname: Stiber
authors.forename: A D
authors.initials: AD
authors.lastname: Lobo
authors.forename: S
authors.initials: S
authors.lastname: Hunsberger
authors.forename: E
authors.initials: E
authors.lastname: Guetta
authors.forename: S E
authors.initials: SE
authors.lastname: Epstein
authors.forename: E F
authors.initials: EF
authors.lastname: Unger
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D016228:Endothelial Growth Factors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects; D008222:Lymphokines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2