title: Protective effects of basic fibroblast growth factor in early atherosclerosis.
abstract: OBJECTIVE
  The role of basic fibroblast growth factor (bFGF) in atherosclerotic plaque formation is incompletely understood. Although it may act as a proatherogenic factor due to its stimulatory effect on smooth muscle cell growth, previous studies have suggested that it may also have beneficial effects by reversing endothelial dysfunction in experimental models. Our purpose was to evaluate the effects of systemic chronic administration of basic FGF on the development of atherosclerotic plaques in a rabbit model.
  
  
  METHODS
  We investigated the effect of bFGF or placebo (2.5 microg IV twice a week), begun on the same day as a cholesterol (2%) diet, and continued for 5 or 10 weeks, on in vitro reactivity, vascular cell adhesion molecule-1 (VCAM-1) expression and plaque development (protocol 1; n = 37). The effects of bFGF or placebo (2.5 microg IV once a week) were also studied in animals fed a 0.2% cholesterol diet and sacrificed at 3 months (protocol 2; n = 18). Results were compared to those of rabbits fed with a normal chow (normal animals).
  
  
  RESULTS
  In protocol 1, bFGF administration for 5 weeks was associated with an improvement in endothelial function (p < 0.05), with a decrease in VCAM-1 expression (p = 0.03) and in the macrophage content of the plaque (p = 0.02). This preventive effect was lost at 10 weeks. In protocol 2, bFGF was associated with similar "beneficial" endpoints as observed at 5 weeks in protocol 1.
  
  
  CONCLUSIONS
  Administration of bFGF is associated with important beneficial structural and functional effects in the early stage of experimental atherosclerosis. These results may help us to understand the role of growth factors in atherosclerosis and to anticipate their effects in human arteries.
authors.affiliation: Centre Hospitalier de Lille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Six
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mouquet
authors.forename: Delphine
authors.initials: D
authors.lastname: Corseaux
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.forename: Thierry
authors.initials: T
authors.lastname: Letourneau
authors.forename: Benoît
authors.initials: B
authors.lastname: Vallet
authors.forename: Christine C
authors.initials: CC
authors.lastname: Dosquet
authors.forename: Bernard
authors.initials: B
authors.lastname: Dupuis
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
authors.forename: Michel E
authors.initials: ME
authors.lastname: Bertrand
authors.forename: Christophe
authors.initials: C
authors.lastname: Bauters
authors.forename: Eric
authors.initials: E
authors.lastname: Van Belle
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000473:pathology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000737:chemistry; D010656:Phenylephrine / Q000737:chemistry; D010919:Placebos; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D007476:Ionophores; D010919:Placebos; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D016222:Fibroblast Growth Factor 2; D009599:Nitroprusside; D010656:Phenylephrine; D002784:Cholesterol; D000109:Acetylcholine; D002118:Calcium