title: α-Tocopherol induces proatherogenic changes to HDL2 & HDL3: an in vitro and ex vivo investigation.
abstract: BACKGROUND
  High density lipoproteins (HDL) have considerable potential for improving cardiovascular health. Additionally, epidemiological studies have identified an inverse relationship between α-tocopherol intake and cardiovascular disease, which has not been translated in randomised controlled trials.
  
  
  OBJECTIVE
  This study assessed if increased α-tocopherol within HDL(2) and HDL(3) (HDL(2&3)) influenced their antiatherogenic potential. In the first of two in vitro investigations, the oxidation potential of HDL(2&3) was assessed when α-tocopherol was added following their isolation. In the second, their oxidation potential was assessed when HDL(2&3) were isolated from serum pre-incubated with α-tocopherol. Additionally, a 6-week placebo-controlled intervention with α-tocopherol assessed if α-tocopherol influenced the oxidation potential and activities of HDL(2&3)-associated enzymes, paraoxonase-1 (PON-1) and lecithin cholesteryl acyltransferase (LCAT).
  
  
  RESULTS
  Conflicting results arose from the in vitro investigations, whereby increasing concentrations of α-tocopherol protected HDL(2&3) against oxidation in the post-incubated HDL(2&3), and promoted HDL(2&3)-oxidation when they were isolated from serum pre-incubated with α-tocopherol. Following the 6-week placebo-controlled investigation, α-tocopherol increased in HDL(2&3), while HDL(2&3) became more susceptible to oxidation, additionally the activities of HDL(2&3)-PON-1 and HDL(2)-LCAT decreased.
  
  
  CONCLUSIONS
  These results have shown for the first time that α-tocopherol induces changes to HDL(2&3), which could contribute to the pathophysiology of cardiovascular disease.
authors.affiliation: Nutrition and Metabolism Group, Centre for Public Health, Queen's University Belfast, Pathology Building, Grosvenor Road, Belfast BT12 6BJ, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Wade
authors.forename: Nida
authors.initials: N
authors.lastname: Nadeem
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Jayne V
authors.initials: JV
authors.lastname: Woodside
authors.forename: Ann
authors.initials: A
authors.lastname: McGinty
authors.forename: Cyril
authors.initials: C
authors.lastname: McMaster
authors.forename: Jane
authors.initials: J
authors.lastname: McEneny
mesh_terms: D000328:Adult; D043303:Aryldialkylphosphatase / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D053439:Lipoproteins, HDL2 / Q000187:drug effects*; D053440:Lipoproteins, HDL3 / Q000187:drug effects*; D008297:Male; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D017382:Reactive Oxygen Species; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D043303:Aryldialkylphosphatase; D024502:alpha-Tocopherol