title: Somatic gene transfer of human ApoA-I inhibits atherosclerosis progression in mouse models.
abstract: BACKGROUND
  Apolipoprotein (apo) A-I is the major component of HDL, and it displays antiatherogenic properties.
  
  
  RESULTS
  The human apoA-I gene has been transferred into different mouse models by use of a recombinant adenovirus under the control of an RSV-LTR promoter (AV RSV apoA-I). Administration of AV RSV apoA-I to C57BL/6 mice resulted in moderate expression of human apoA-I for 3 weeks, leading to a transient elevation (40% at day 11 after injection) of HDL cholesterol concentration. In contrast, administration of AV RSV apoA-I to human apoA-I-transgenic mice induced a large increase of human apoA-I and HDL cholesterol concentrations (300% and 360%, respectively, at day 14 after injection) for 10 weeks, indicating that an immune response to the transgene was one major hurdle for long-term duration of expression. Recombinant adenovirus expressing human apolipoprotein A-I (AV RSV apoA-I) was also injected into human apoA-I-transgenic/apoE-deficient mice, which are prone to develop atherosclerosis. Over a 6-week period, overexpression of human apoA-I inhibited fatty streak lesion formation by 56% in comparison with control.
  
  
  CONCLUSIONS
  Somatic gene transfer of human apoA-I prevents the development of atherosclerosis in the mouse model.
authors.affiliation: Rhône-Poulenc Rorer-Gencell Division, Cardiovascular Department, Centre de recherche de Vitry-Alfortville, Vitry sur Seine, France.
authors.forename: P
authors.initials: P
authors.lastname: Benoit
authors.forename: F
authors.initials: F
authors.lastname: Emmanuel
authors.forename: J M
authors.initials: JM
authors.lastname: Caillaud
authors.forename: L
authors.initials: L
authors.lastname: Bassinet
authors.forename: G
authors.initials: G
authors.lastname: Castro
authors.forename: P
authors.initials: P
authors.lastname: Gallix
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: D
authors.initials: D
authors.lastname: Branellec
authors.forename: P
authors.initials: P
authors.lastname: Denèfle
authors.forename: N
authors.initials: N
authors.lastname: Duverger
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000628:therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E