Endothelial lipase increases antioxidative capacity of high-density lipoprotein

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Oct;1864(10):1363-1374. doi: 10.1016/j.bbalip.2019.06.011. Epub 2019 Jun 17.


Endothelial lipase (EL) is a strong determinant of structural and functional properties of high-density lipoprotein (HDL). We examined whether the antioxidative capacity of HDL is affected by EL. EL-modified HDL (EL-HDL) and control EV-HDL were generated by incubation of HDL with EL- overexpressing or control HepG2 cells. As determined by native gradient gel electrophoresis, electron microscopy, and small-angle X-ray scattering EL-HDL is smaller than EV-HDL. Mass spectrometry revealed an enrichment of EL-HDL with lipolytic products and depletion of phospholipids and triacylglycerol. Kinetics of conjugated diene formation and HPLC-based malondialdehyde quantification revealed that EL-HDL exhibited a significantly higher resistance to copper ion-induced oxidation and a significantly higher capacity to protect low-density lipoprotein (LDL) from copper ion-induced oxidation when compared to EV-HDL. Depletion of the lipolytic products from EL-HDL abolished the capacity of EL-HDL to protect LDL from copper ion-induced oxidation, which could be partially restored by lysophosphatidylcholine enrichment. Proteomics of HDL incubated with oxidized LDL revealed significantly higher levels of methionine 136 sulfoxide in EL-HDL compared to EV-HDL. Chloramine T (oxidizes methionines and modifies free thiols), diminished the difference between EL-HDL and EV-HDL regarding the capacity to protect LDL from oxidation. In absence of LDL small EV-HDL and EL-HDL exhibited higher resistance to copper ion-induced oxidation when compared to respective large particles. In conclusion, the augmented antioxidative capacity of EL-HDL is primarily determined by the enrichment of HDL with EL-generated lipolytic products and to a lesser extent by the decreased HDL particle size and the increased activity of chloramine T-sensitive mechanisms.

Keywords: HDL; LDL; Mass spectrometry; Oxidation; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Copper / metabolism
  • Female
  • Hep G2 Cells
  • Humans
  • Lipase / metabolism*
  • Lipoproteins, HDL / metabolism*
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress


  • Lipoproteins, HDL
  • Copper
  • LIPG protein, human
  • Lipase