title: Vitamin E induces phosphatidylserine externalization and red cell adhesion to endothelial cells.
abstract: Red blood cell (RBC) adhesion to vessel wall endothelium is a potent catalyst of vascular occlusion and occurs in oxidative stress states such as hemoglobinopathies and cardiovascular conditions. These are often treated with vitamin E (VitE), a "classic" antioxidant. In this study, we examined the effects of VitE on RBC adhesion to vascular endothelial cells (EC), and on translocation of phosphatidylserine (PS) to RBC surface, known as a potent mediator of RBC/EC adhesion, facilitating thrombus formation. Treatment of RBC with VitE strongly induces (up to sevenfold) PS externalization and enhances (up to 20-fold) their adherence to EC. The VitE hydrophilic analogue-Trolox-does not incorporate into cell membranes. Trolox did not exhibit any of these effects, implying that the VitE effect is due to its known ability to incorporate into cell membranes. The membrane-incorporated VitE significantly reduced the level of reactive oxygen species in H(2)O(2)-treated RBC, demonstrating that VitE elevates RBC/EC adhesion despite acting as an anti-oxidant. This study demonstrates for the first time that contrary to the common view of VitE as a beneficial supplement, VitE may introduce a circulatory risk by inducing flow-disturbing RBC adherence to blood vessel wall and the pro-thrombotic PS exposure.
authors.affiliation: Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koshkaryev
authors.forename: Gregory
authors.initials: G
authors.lastname: Barshtein
authors.forename: Saul
authors.initials: S
authors.lastname: Yedgar
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000166:cytology; D010718:Phosphatidylserines / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D010718:Phosphatidylserines; D014810:Vitamin E