Increased Atherosclerotic Lesions in ApoE Mice With Plasma Phospholipid Transfer Protein Overexpression

X. P. Yang
2003 Arteriosclerosis, Thrombosis and Vascular Biology  
Objective-Plasma phospholipid transfer protein (PLTP) is involved in the metabolism of HDL and apolipoprotein B (apoB)-containing lipoproteins. Atherosclerosis susceptibility is decreased in mice with PLTP deficiency that is associated with decreased liver production of apoB-containing lipoproteins and increase in their antioxidant. To investigate additionally the effect of PLTP on the development of atherosclerosis, we overexpressed PLTP in mice. Methods and Results-PLTP was overexpressed in
more » ... overexpressed in apoE knockout mice using an adenovirus-associated virus (AAV)mediated system. Plasma PLTP activity was 1.3-to 2-fold higher in mice injected with AAV-PLTP than in mice injected with control AAV-GFP, and PLTP levels were sustained during the experiment period (4 months). We show that 2-fold increased PLTP activity results in (1) a decrease in HDL cholesterol, HDL phospholipid, and apoAI levels; (2) a decrease in vitamin E contents in total plasma and in individual lipoprotein fractions; (3) an increase in lipoprotein oxidizability as assessed by copper-induced formation of conjugated dienes; (4) an increase in autoantibodies against oxidized apoB-containing particles; and (5) an increase in atherosclerosis lesions in proximal aorta. Conclusions-These observations indicate that elevated plasma PLTP levels constitute a novel, long-term risk factor for atherosclerosis. (Arterioscler Thromb Vasc Biol. 2003;23:1601-1607.)
doi:10.1161/01.atv.0000085841.55248.13 pmid:12855484 fatcat:qi7c6zyoj5bw3e7utsyampad7y