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on October 12, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print October 12, 2006, doi: 10.1161/01.ATV.0000249721.96666.e5
A more recent version of this article appeared on January 1, 2007
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Submitted on April 14, 2006
Accepted on September 20, 2006

Macrophage Phospholipid Transfer Protein Deficiency and ApoE Secretion. Impact on Mouse Plasma Cholesterol Levels and Atherosclerosis

Ruijie Liu ; Mohammad R. Hojjati ; Cecilia M. Devlin ; Inge H. Hansen ; and Xian-Cheng Jiang *

From the Department of Anatomy and Cell Biology (R.L., M.R.H., X.C.J.), SUNY Downstate Medical Center, Brooklyn, and the Department of Medicine (C.M.D., I.H.H.), Columbia University, New York.

* To whom correspondence should be addressed. E-mail: xjiang{at}downstate.edu.

Objective--PLTP and apoE play important roles in lipoprotein metabolism and atherosclerosis. It is known that formation of macrophage-derived foam cells (which highly express PLTP and apoE) is the critical step in the process of atherosclerosis. We investigated the relationship between PLTP and apoE in macrophages and the atherogenic relevance in a mouse model.

Methods and Results--We transplanted PLTP-deficient mouse bone marrow into apoE-deficient mice (PLTP-/-->apoE-/-), creating a mouse model with PLTP deficiency and apoE expression exclusively in the macrophages. We found that PLTP-/-->apoE-/- mice have significantly lower PLTP activity, compared with controls (WT->apoE-/-; 20%, P<0.01). On a Western type diet, PLTP-/-->apoE-/- mice have significantly lower plasma apoE than that of WT->apoE-/- mice (63%, P<0.001), and PLTP-deficient macrophages secrete significantly less apoE than WT macrophages (44%, P<0.01). Moreover, PLTP-/-->apoE-/- mice have significantly higher plasma cholesterol (98%, P<0.001) and phospholipid (107%, P<0.001) than that of WT->apoE-/- mice, thus increasing atherosclerotic lesions in the aortic arch and root (403%, P<0.001), as well as the entire aorta (298%, P<0.001).

Conclusions--Macrophage PLTP deficiency causes a significant reduction of apoE secretion from the cells, and this in turn promotes the accumulation of cholesterol in the circulation and accelerates the development of atherosclerosis.
Key words: phospholipid transfer protein • apoE • bone marrow transplantation • macrophage • lipoprotein • atherosclerosis




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