期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 26, 期 9, 页码 2160-2167出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000235699.98024.11
关键词
antioxidants; lipoproteins; tocopherol; phospholipid transfer protein; mice
Objective - The aim of the present study was to assess the effect of alpha-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 alpha-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 alpha-and gamma-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 alpha-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.
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