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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2407.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cholesterol Accumulation Is Increased in Macrophages of Phospholipid Transfer Protein-Deficient Mice

Normalization by Dietary Alpha-Tocopherol Supplementation

Nicolas Ogier; Alexis Klein; Valérie Deckert; Anne Athias; Ginette Bessède; Naig Le Guern; Laurent Lagrost; Catherine Desrumaux

From INSERM U866, Centre de Recherche INSERM, IFR Santé-STIC, Faculté de Médecine, Université de Bourgogne, Dijon, France.

Correspondence to Dr Catherine Desrumaux/Dr Laurent Lagrost, INSERM U866 - Faculté de Médecine, 7, Bd Jeanne d’Arc BP 87900, 21079 DIJON Cedex, France. E-mail Catherine.Desrumaux{at}u-bourgogne.fr or Laurent.Lagrost@u-bourgogne.fr

Objective— Phospholipid transfer protein (PLTP) is a multifunctional, extracellular lipid transport protein that plays a major role in lipoprotein metabolism and atherosclerosis. Recent in vivo studies suggested that unlike systemic PLTP, macrophage-derived PLTP would be antiatherogenic. The present study aimed at characterizing the atheroprotective properties of macrophage-derived PLTP.

Methods and Results— Peritoneal macrophages were isolated from PLTP-deficient and wild-type mice and their biochemical characteristics were compared. It is shown that macrophages isolated from PLTP-deficient mice have increased basal cholesterol content and accumulate more cholesterol in the presence of LDL compared with wild-type cells. Cholesterol parameters in macrophages of PLTP-deficient mice were normalized by dietary -tocopherol supplementation.

Conclusions— The antiatherogenic properties of macrophage-derived PLTP are related at least in part to its ability to reduce cholesterol accumulation in macrophages through changes in the -tocopherol content and oxidative status of the cells.

Although systemic PLTP is proatherogenic, recent findings suggested that macrophage-derived PLTP could be antiatherogenic. This study shows that the reduced -tocopherol content of isolated macrophages from PLTP-deficient mice is associated with increased cholesterol accumulation in these cells. Cholesterol parameters in the macrophages of PLTP-deficient mice were normalized by dietary supplementation with -tocopherol.

Key Words: phospholipid transfer protein • vitamin E • tocopherol • macrophage

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