Published online before print July 6, 2006, doi: 10.1161/01.ATV.0000235699.98024.11
© 2006 American Heart Association, Inc.
Thrombosis |
-Tocopherol Modulates Phosphatidylserine Externalization in Erythrocytes
Relevance in Phospholipid Transfer Protein–Deficient Mice
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
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