High density lipoprotein subfractions: isolation, composition, and their duplicitous role in oxidation

Peter McPherson, Ian Young, Bronac McKibben, Jane McEneny

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66 Citations (Scopus)


The plasma HDLs represent a major class of cholesterol-transporting lipoprotein that can be divided into two distinct subfractions, HDL2 and HDL3, by ultracentrifugation. Existing methods for the subfractionation of HDL requires lengthy ultracentrifugations, making them unappealing for large-scale studies. We describe a method that subfractionates HDL from plasma in only 6 h, representing a substantial decrease in total isolation time. The subfractions so isolated were assessed for a variety of lipid and protein components, in addition to their susceptibility to oxidation, both alone and in combination with VLDL and LDL. We report for the first time a prooxidant role for HDL during VLDL oxidation, in which HDL donates preformed hydroperoxides to VLDL in a cholesteryl ester transfer protein (CETP)-dependent process. Examination of the participation of HDL in LDL oxidation has reinforced its classic role as a potent antioxidant. Furthermore, we have also implicated the second major HDL-associated enzyme, LCAT, in these processes, whereby it acts as a potent prooxidant during VLDL oxidation but as an antioxidant during LDL oxidation. Thus, we have identified a potentially duplicitous role for HDL in the pathogenesis of atherosclerosis, attributable to both CETP and LCAT.
Original languageEnglish
Pages (from-to)86-98
Number of pages10
JournalJournal of Lipid Research
Issue number1
Publication statusPublished (in print/issue) - Jan 2007


  • apolipoproteins
  • cholesteryl ester transfer protein
  • & lecithin:cholesterol acyltransferase
  • lipid hydroperoxides
  • single radial immunodiffusion
  • transferrin
  • ultracentrifugation


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