Somatic gene transfer of human ApoA-I inhibits atherosclerosis progression in mouse models.
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.
Benoit
P
P
Rhône-Poulenc Rorer-Gencell Division, Cardiovascular Department, Centre de recherche de Vitry-Alfortville, Vitry sur Seine, France.
Emmanuel
F
F
Caillaud
J M
JM
Bassinet
L
L
Castro
G
G
Gallix
P
P
Fruchart
J C
JC
Branellec
D
D
Denèfle
P
P
Duverger
N
N
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
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E