This Article Full Text Full Text (PDF) All Versions of this Article: 26/9/2160    most recent 01.ATV.0000235699.98024.11v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klein, A. Articles by Lagrost, L. Search for Related Content PubMed PubMed Citation Articles by Klein, A. Articles by Lagrost, L.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2160.)
© 2006 American Heart Association, Inc.

Thrombosis

-Tocopherol Modulates Phosphatidylserine Externalization in Erythrocytes

Relevance in Phospholipid Transfer Protein–Deficient Mice

Alexis Klein; Valérie Deckert; Martina Schneider; Fabienne Dutrillaux; Arlette Hammann; Anne Athias; Naig Le Guern; Jean-Paul Pais de Barros; Catherine Desrumaux; David Masson; Xian-Cheng Jiang; Laurent Lagrost

From INSERM U498 (A.K., V.D., M.S., A.A., N.L.G., J.-P.P.d.B., C.D., D.M., L.L.) and INSERM U517 (A.H.), IFR100, Université de Bourgogne, Dijon, France; Service d’Hématologie (F.D.), CHU Dijon, France; and Downstate Medical Center (X.-C.J), State University of New York.

Correspondence to Laurent Lagrost, PhD, INSERM U498, Faculté de Médecine, 7 Boulevard Jeanne d’Arc, BP 87900, 21079 Dijon Cedex, France. E-mail laurent.lagrost{at}u-bourgogne.fr

Objective— The aim of the present study was to assess the effect of -tocopherol, the main vitamin E isomer on phosphatidylserine (PS) exposure at the surface of circulating erythrocytes, and to determine consequences on erythrocyte properties.

Methods and Results— In vitro -tocopherol enrichment of isolated erythrocytes significantly decreased PS externalization as assessed by lower Annexin V-fluorescein isothiocyanate labeling. Plasma phospholipid transfer protein (PLTP) transfers vitamin E, and both -and -tocopherol accumulated in circulating erythrocytes from PLTP-deficient homozygous (PLTP^–/–) mice as compared with wild-type mice. In agreement with in vitro studies, vitamin E–enriched erythrocytes from PLTP^–/– mice displayed fewer externalized PS molecules than wild-type controls (–64%, P<0.05). The perturbation of phospholipid membrane asymmetry from PLTP^–/– erythrocytes was accompanied by impairment of their procoagulant properties, with a 20% increase in clotting time as compared with wild-type controls (P<0.05). Less pronounced, however still significant, changes were observed in -tocopherol content, procoagulant properties, and PS externalization in erythrocytes of PLTP-deficient heterozygotes. Finally, whole blood coagulation and circulating level of D-dimer, which reflects increased thrombus formation in vivo, were significantly decreased in PLTP^–/– mice compared with wild-type mice.

Conclusions— Vitamin E modifies PS externalization in circulating erythrocytes, thus modulating in vivo their PS-dependent procoagulant properties.

In vitro -tocopherol enrichment of isolated erythrocytes, as well as accumulation of -tocopherol in circulating erythrocytes of phospholipid transfer protein–deficient mice, led to fewer externalized phosphatidylserine molecules. This was associated with impaired procoagulant activity, and lower circulating levels of D-dimer, which is known to reflect thrombus formation in vivo.

Key Words: antioxidants • lipoproteins • tocopherol • phospholipid transfer protein • mice

This article has been cited by other articles:

				T. Gautier, A. Klein, V. Deckert, C. Desrumaux, N. Ogier, A.-L. Sberna, C. Paul, N. Le Guern, A. Athias, T. Montange, et al. Effect of Plasma Phospholipid Transfer Protein Deficiency on Lethal Endotoxemia in Mice J. Biol. Chem., July 4, 2008; 283(27): 18702 - 18710. [Abstract] [Full Text] [PDF]

				N. Ogier, A. Klein, V. Deckert, A. Athias, G. Bessede, N. Le Guern, L. Lagrost, and C. Desrumaux Cholesterol Accumulation Is Increased in Macrophages of Phospholipid Transfer Protein-Deficient Mice: Normalization by Dietary Alpha-Tocopherol Supplementation Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2407 - 2412. [Abstract] [Full Text] [PDF]