Abstract 10991: Human Apolipoprotein Aii Protects Against Diet-induced Atherosclerosis in Transgenic Rabbits

Abstract

Background- Apolipoprotein AII (apo A-II) is the second major apolipoprotein of HDLs but its pathophysiological roles in the development of atherosclerosis remain elusive.

Methods and Results - To examine the hypothesis that apo A-II may affect atherogenesis, we compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates although plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells and apo A-II immune-reactive proteins were frequently detected in the lesions. HDLs of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than HDLs isolated from non-Tg rabbits. In addition, β-VLDL of Tg rabbits were less sensitive to copper-induced oxidization than β-VLDL of non-Tg rabbits.

Conclusions- These results suggest that enrichment of apo A-II in HDL particles has atheroprotective effects in vivo and apo A-II may become a possible target for the treatment of atherosclerosis.