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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1601.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Xiao Ping Yang; Daoguang Yan; Chunping Qiao; Rui Jie Liu; Jer-Gin Chen; Juan Li; Martina Schneider; Laurent Lagrost; Xiao Xiao; Xian-Cheng Jiang

From the Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center (X.P.Y., D.Y., R.J.L., J.C., X.C.J.), Brooklyn, NY; Department of Molecular Genetics and Biochemistry, University of Pittsburgh (C.Q., J.L., X.X.), Pittsburgh, Pa; and INSERM U498, Faculté de Médecine (M.S., L.L.), Dijon, France.

Correspondence to Xian-Cheng Jiang, PhD, Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203. E-mail xjiang{at}downstate.edu

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 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.

Key Words: phospholipid transfer protein • apoB-containing lipoproteins • oxidation • high-density lipoprotein • atherosclerosis

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