on July 6, 2006
Published online before print July 6, 2006, doi: 10.1161/01.ATV.0000235699.98024.11
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 14, 2006
Accepted on June 14, 2006
-Tocopherol Modulates Phosphatidylserine Externalization in Erythrocytes. Relevance in Phospholipid Transfer Protein-Deficient Mice
Alexis Klein ;
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.
* To whom correspondence should be addressed. 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.
Key words: antioxidants • lipoproteins • tocopherol • phospholipid transfer protein • mice
This article has been cited by other articles:
 |
|
 |
|
  C. Oslakovic, M. J. Krisinger, A. Andersson, M. Jauhiainen, C. Ehnholm, and B. Dahlback Anionic Phospholipids Lose Their Procoagulant Properties When Incorporated into High Density Lipoproteins J. Biol. Chem., February 27, 2009; 284(9): 5896 - 5904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|