Paraoxonase 1 protects macrophages from atherogenicity of a specific triglyceride isolated from human carotid lesion

Hagai Tavori, Michael Aviram, Soliman Khatib, Ramadan Musa, Dalit Mannheim, Ron Karmeli, Jacob Vaya

    Research output: Contribution to journalArticlepeer-review

    26 Scopus citations

    Abstract

    Human atherosclerotic lesions contain oxidized lipids that facilitate further oxidation of macrophages, LDLs, and oxidative stress (OS)-sensitive markers and inhibit the antiatherogenic enzyme paraoxonase 1 (PON1). Our aim was to isolate and identify the oxidizing agent in a human atherosclerotic lesion lipid extract (LLE) and to explore the mechanisms of oxidation and of PON1's effect on the oxidizing agent. Of the five main fractions separated from the LLE, only fraction 2 (F2) promoted macrophage reactive oxygen species (ROS) production via a mechanism requiring mitochondrial involvement, whereas the NADPH oxidase system was not involved. Incubation of F2 with PON1 abridged the former's peroxide value and reduced its capacity to oxidize OS markers. The active agent was a triglyceride composed of palmitic, oleic, and linoleic acids, with 0.3% of its linoleic moiety in oxidized form. Incubation of either F2 or an identical synthetic triglyceride with PON1 reduced their ability to oxidize macrophages, without affecting cellular accumulation of triglycerides. We conclude that macrophage ROS production by LLE occurs in the presence of a specific triglyceride and requires mitochondrial involvement. Lipid peroxide in the triglyceride can also facilitate lipid autoxidation. Both atherogenic pathways are suppressed by PON1, which acts as an antiatherogenic element.

    Original languageEnglish (US)
    Pages (from-to)234-242
    Number of pages9
    JournalFree Radical Biology and Medicine
    Volume51
    Issue number1
    DOIs
    StatePublished - Jul 1 2011

    Keywords

    • Atherosclerosis
    • Carotid lesion
    • Free radicals
    • Oxidative stress
    • Paraoxonase 1
    • Triglyceride

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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