Plasma HDL reduces nonesterified fatty acid hydroperoxides originating from oxidized LDL: A mechanism for its antioxidant ability

Mari Kotosai, Sachiko Shimada, Mai Kanda, Namiko Matsuda, Keiko Sekido, Yoshibumi Shimizu, Akira Tokumura, Toshiyuki Nakamura, Kaeko Murota, Yoshichika Kawai, Junji Terao

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


The antioxidant property of plasma high-density lipoprotein (HDL) is thought to be involved in potential anti-atherogenic effects but the exact mechanism is not known. We aimed to reveal the contribution of HDL on the elimination of lipid hydroperoxides (LOOH) derived from oxidized low-density lipoprotein (LDL). Oxidized LDL prepared by copper ion-induced oxidation contained nonesterified fatty acid hydroperoxides (FFA-OOH) and lysophosphatidylcholine (lysoPtdCho), in addition to cholesteryl ester hydroperoxides (CE-OOH) and phosphatidylcholine hydroperoxides (PtdCho-OOH). A platelet-activating factor-acetylhydrolase (PAF-AH) inhibitor suppressed formation of FFA-OOH and lysoPtdCho in oxidized LDL. Among LOOH species, FFA-OOH was preferentially reduced by incubating oxidized LDL with HDL. HDL exhibited selective FFA-OOH reducing ability if it was mixed with a liposomal solution containing FFA-OOH, CE-OOH and PtdCho-OOH. Two-electron reduction of the hydroperoxy group to the hydroxy group was confirmed by the formation of 13-hydroxyoctadecadienoic acid from 13-hydroperoxyoctadecadienoic acid in HPLC analyses. This reducing effect was also found in apolipoprotein A-1 (apoA-1). FFA-OOH released from PtdCho-OOH due to PAF-AH activity in oxidized LDL undergo two-electron reduction by the reducing ability of apoA1 in HDL. This preferential reduction of FFA-OOH may participate in the mechanism of the antioxidant property of HDL.

Original languageEnglish
Pages (from-to)569-578
Number of pages10
Issue number6
Publication statusPublished - Jun 2013
Externally publishedYes


  • Apolipoprotein A-1
  • Atherosclerosis
  • HDL
  • Nonesterified fatty acid hydroperoxides
  • Oxidized LDL
  • Platelet activating factor-acetyl hydrolase

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology


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