出版社：American Society for Biochemistry and Molecular Biology
摘要：Transgenic (Tg) mice that overexpress the human apolipoprotein A-V gene ( APOA5 ) yet lack an endogenous mouse apoa5 gene ( APOA5 Tg mice) were generated. Subsequently, the effect of human apoA-V expression on plasma triglyceride (TG) concentration and lipoprotein and apolipoprotein distribution was determined and compared with that in mice deficient in apoA-V ( apoa5 −/− mice). NMR analysis of plasma lipoproteins revealed that APOA5 Tg mice had a very low VLDL concentration (26.4 ± 7.7 nmol/dl), whereas VLDL in apoa5 −/− mice was 18- fold higher (467 ± 152 nmol/dl). SDS-PAGE analysis of the d APOA5 Tg versus apoa5 −/− mice and that the apoE/total apoB ratio was 7-fold greater in APOA5 Tg versus apoa5 −/− mice. It is anticipated that a reduction in apoB-100/apoB-48 ratio as well as that for apoE/apoB would impair the uptake of VLDL and remnants in apoa5 −/− mice, thereby contributing to increased plasma TG levels. The concentration of apoA-V in APOA5 Tg mice was 12.5 ± 2.9 μg/ml, which is ∼50- to 100-fold higher than that reported for normolipidemic humans. ApoA-V was predominantly associated with HDL but was rapidly and efficiently redistributed to apoA- V-deficient VLDL upon incubation. Consistent with findings reported for human subjects, apoA-V concentration was positively correlated with TG levels in normolipidemic APOA5 Tg mice. It is conceivable that, in a situation in which apoA-V is chronically overexpressed, complex interactions among factors regulating TG homeostasis may result in a positive correlation of apoA-V with TG concentrations.
