It is now well known that oxidation of lipids and lipoproteins have immense effects on the development of atherosclerosis. Since hydroperoxides are the major products of lipid peroxidation, its identification and measurement can provide valuable information, including primary prevention of coronary heart disease (CHD). Despite its importance, laboratory determination of hydroperoxides in biological samples has been considered to be arduous because of their trace concentration, instability and molecular diversity. Most importantly, we do not have much detail about the molecular species of such hydroperoxides that exist in human plasma. Identification of hydroperoxides species of cholesteryl esters, phospholipids, and triglycerides are largely limited in artificially oxidized lipoproteins. Our group has identified several hydroperoxides in oxidatively modified lipoproteins. Some also exist in plasma and the unmodified lipoproteins fractions (1-3).

Several triglyceride hydroperoxides (TGOOH) have been shown to exist in the normal plasma only on oxidatively-modified, but not native, LDL and HDL (4). Using liquid chromatography/LTQ ion trap mass spectrometry/Orbitrap high-mass-accuracy mass spectrometry, we detected and characterized 11 molecular species of TGOOH existing in plasma, each contributed by triglyceride-rich lipoproteins (TGRLP), including VLDL and IDL.

Elevated triglyceride concentrations in blood are an independent risk factor for CHD, and individuals with high triglycerides should begin strategies to reduce this risk. Though the TGOOH fraction makes up a small portion of total serum triglycerides, can it contribute to the risk associated with elevated serum triglycerides? Although controversial, various epidemiological, clinical and experimental studies have highlighted the atherogenicity of TGRLP. Our study found that TGOOH are solely carried by the TGRLP, leading us to ask, Can these TGOOH then contribute to the atherogenicity of TGRLP? If TGOOH contributes to atherogenesis, can it be a biomarker for future coronary events?

  1. Shrestha R, Hui SP, Sakurai T, Yagi A, Takahashi Y, Takeda S, et al. Identification of molecular species of cholesteryl ester hydroperoxides in very low-density and intermediate-density lipoproteins. Anal Clin Biochem (Accepted Sept 15, 2013).
  3. Hui SP, Sakurai T, Ohkawa F, Furumaki H, Jin S, Fuda H, et al. Detection and characterization of cholesteryl ester hydroperoxides in oxidized LDL and oxidized HDL by use of an Orbitrap mass spectrometer. Anal Bioanal Chem 2012;404:101-12.
  5. Hui SP, Taguchi Y, Takeda S, Ohkawa F, Sakurai T, Yamaki S, et al. Quantitative determination of phosphatidylcholine hydroperoxides during copper oxidation of LDL and HDL by liquid chromatography/mass spectrometry. Anal Bioanal Chem 2012;403:1831-40.
  7. Hui SP, Sakurai T, Takeda S, Jin S, Fuda H, Kurosawa T, et al. Analysis of triacylglycerol hydroperoxides in human lipoproteins by Orbitrap mass spectrometer. Anal Bioanal Chem 2013:405;4981-7.

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