Plasma phospholipid transfer protein prevents vascular endothelium dysfunction by delivering alpha-tocopherol to endothelial cells

alpha-tocopherol, the most potent antioxidant form of vitamin E, is mainly bound to lipoproteins in plasma and its incorporation into the vascular wal l can prevent the endothelium dysfunction at an early stage of atherogenesi s. In the present study, the plasma phospholipid transfer protein (PLTP) wa s shown to promote the net mass transfer of alpha-tocopherol from high dens ity lipoproteins (HDL) and alpha-tocopherol-albumin complexes toward alpha- tocopherol-depleted, oxidized low density lipoproteins (LDL). The facilitat ed transfer reaction of alpha-tocopherol could be blocked by specific anti- PLTP antibodies. These observations indicate that PLTP may restore the anti oxidant potential of plasma LDL at an early stage of the oxidation cascade that subsequently leads to cellular damages. In addition, the present study demonstrated that the PLTP-mediated net mass transfer of alpha-tocopherol can constitute a new mechanism for the incorporation of alpha-tocopherol in to the vascular wall in addition to the previously recognized LDL receptor and lipoprotein lipase pathways. In ex vivo studies on rabbit aortic segmen ts, the impairment of the endothelium-dependent arterial relaxation induced by oxidized LDL was found to be counteracted by a pretreatment with purifi ed PLTP and alpha-tocopherol-albumin complexes, and both the maximal respon se and the sensitivity to acetylcholine were significantly improved. We con clude that PLTP, by supplying oxidized LDL and endothelial cells with alpha -tocopherol through a net mass transfer reaction may play at least two dist inct beneficial roles in preventing endothelium damage, i.e., the antioxida nt protection of LDL and the preservation of a normal relaxing function of vascular endothelial cells.