Somatic gene transfer of human apoA-I inhibits atherosclerosis progressionin mouse models

Background-Apolipoprotein (apo) A-I is the major component of HDL, and it d isplays antiatherogenic properties. Methods ann Results-The human apoA-I gene has been transferred into differe nt 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 cholestero l concentration. In contrast, administration of AV RSV apoA-I to human apnA -I-transgenic mice induced a large increase of human apoA-I and HDL cholest erol 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 adenavirus 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 ath erosclerosis. Over a 6-week period, overexpression of human apoA-I inhibite d 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.