Subject The Effect of Apolipoprotein E Overexpression on Plasma Lipoprotein Profile in Mice Fed on Long-term High Cholesterol Diet

ABSTRACT

BACKGROUND AND OBJECTIVES: Apolipoprotein E (apoE), a 34-kD plasma glycoapolipoprotein, plays a key role in lipoprotein metabolism by facilitating cellular uptake of remnants of triglyceride-rich chylomicrons and VLDL and may have other important biological functions. Various studies using apoE-knockout mice have elucidated the role of apoE in lipolysis, remnant clearance, and atherogenesis. Despite the growing evidence of the protective role exerted by apoE against atherosclerosis, the direct in vivo effects of the apoE overexpression on lipoprotein metabolism in the presence of endogenous mouse apoE are not yet fully understood. In this study, the technique of adenovirus-mediated gene transfer was employed to investigate the in vivo effect of apoE overexpression on lipid level and lipoprotein profile in mice fed on normal chow or high cholesterol diet. MATERIALS AND METHODS: Recombinant adenovirus (rAd.mApoE) containing mouse apoE cDNA driven by a cytomegalovirus promoter was generated and infused via tail vein in mice fed on normal chow or high cholesterol diet. Recombinant adenoviruses have emerged as the most efficient vectors for transient delivery of functional genes to the mammalian liver. RESULTS: rAd.mApoE in the various mouse tissues one week after injection was expressed mainly in the liver. ApoE overexpression decreased the cholesterol and triglyceride concentration in mice fed on normal chow. In mice fed on high cholesterol diet, apoE overexpression resulted in decrease in triglyceride concentration and increase in cholesterol. VLDL and LDL fraction were decreased, HDL was increased by apoE overexpression in both mice fed on normal chow and high cholesterol diet. CONCLUSION: These data suggest that overexpression of mouse apoE in mice with endogenous apoE may exert antiatherogenic effect by inducing favorable change in the lipoprotein profile, regardless of diet and consequent plasma lipid level. In the future, the studies regarding the effect of human apoE overexpression on the lipid and lipoprotein profile in mice fed on normal chow and high cholesterol diet will be helpful to understand the species differences or similarities in apoE activity.