Endothelial lipase increases antioxidative capacity of high-density lipoprotein

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1864; no. 10; pp. 1363 - 1374
• Main Authors: Schilcher, Irene, Ledinski, Gerhard, Radulović, Snježana, Hallström, Seth, Eichmann, Thomas, Madl, Tobias, Zhang, Fangrong, Leitinger, Gerd, Kolb-Lenz, Dagmar, Darnhofer, Barbara, Birner-Gruenberger, Ruth, Wadsack, Christian, Kratky, Dagmar, Marsche, Gunther, Frank, Saša, Cvirn, Gerhard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019
• Subjects: Adult; Copper - metabolism; Female; HDL; Hep G2 Cells; Humans; LDL; Lipase - metabolism; Lipoproteins, HDL - metabolism; Male; Mass spectrometry; Middle Aged; Oxidation; Oxidation-Reduction; Oxidative Stress; Proteomics; FFA; LPE; PAF-AH; PON1; LCAT; LysoPL; MDA; HDL-C; HDL; BSA; LDL; NEFA; SM; Oxidation; HPLC; FPLC; CE; HSPG; EL; DAG; SAXS; Cer; EV; PC; PE; FCS; Proteomics; PI; TAG; PL; FC; Met; Mass spectrometry; apoA-I; LPC
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2019.06.011

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. •We examined antioxidative capacity of endothelial lipase modified HDL (EL-HDL).•EL-HDL was smaller and enriched with lipolytic products compared to control HDL.•EL-HDL exhibited increased resistance to copper ion-induced oxidation.•EL-HDL exhibited increased capacity to protect LDL from copper ion-induced oxidation.•Enriched lipolytic products underlie the increased antioxidative capacity of EL-HDL.