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. Methods and 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.