title: Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E.
abstract: Vitamin E is a lipophilic anti-oxidant that can prevent the oxidative damage of atherogenic lipoproteins. However, human trials with vitamin E have been disappointing, perhaps related to ineffective levels of vitamin E in atherogenic apoB-containing lipoproteins. Phospholipid transfer protein (PLTP) promotes vitamin E removal from atherogenic lipoproteins in vitro, and PLTP deficiency has recently been recognized as an anti-atherogenic state. To determine whether PLTP regulates lipoprotein vitamin E content in vivo, we measured alpha-tocopherol content and oxidation parameters of lipoproteins from PLTP-deficient mice in wild type, apoE-deficient, low density lipoprotein (LDL) receptor-deficient, or apoB/cholesteryl ester transfer protein transgenic backgrounds. In all four backgrounds, the vitamin E content of very low density lipoprotein (VLDL) and/or LDL was significantly increased in PLTP-deficient mice, compared with controls with normal plasma PLTP activity. Moreover, PLTP deficiency produced a dramatic delay in generation of conjugated dienes in oxidized apoB-containing lipoproteins as well as markedly lower titers of plasma IgG autoantibodies to oxidized LDL. The addition of purified PLTP to deficient plasma lowered the vitamin E content of VLDL plus LDL and normalized the generation of conjugated dienes. The data show that PLTP regulates the bioavailability of vitamin E in atherogenic lipoproteins and suggest a novel strategy for achieving more effective concentrations of anti-oxidants in lipoproteins, independent of dietary supplementation.
authors.affiliation: Downstate Medical Center, State University of New York, New York, New York 11203, USA.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.forename: Alan R
authors.initials: AR
authors.lastname: Tall
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Martina
authors.initials: M
authors.lastname: Schneider
authors.forename: Florent
authors.initials: F
authors.lastname: Lalanne
authors.forename: Valéerie
authors.initials: V
authors.lastname: Deckert
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood*
chemical_list: D002352:Carrier Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008074:Lipoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D014280:Triglycerides; D014810:Vitamin E; D002784:Cholesterol; D017301:Ca(2+) Mg(2+)-ATPase