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Biochim Biophys Acta Mol Cell Biol Lipids. 2019 May;1864(5):643-653. doi: 10.1016/j.bbalip.2019.01.005. Epub 2019 Jan 12.

Glycosylation of human plasma lipoproteins reveals a high level of diversity, which directly impacts their functional properties.

Author information

1
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia; National Institute for Health and Medical Research (INSERM), UMR 1166 ICAN, Paris F-75013, France; Sorbonne University, Paris F-75013, France; AP-HP, Groupe hospitalier Pitié-Salpétrière, Paris F-75013, France; Federal State Budget Institution of Sciences Institute of Gene Biology, Russian Academy of Sciences, Vavilova Str., 34/5, Moscow 119334, Russia.
2
Genos Glycoscience Research Laboratory, Borongajska cesta 83H, HR-10 000 Zagreb, Croatia.
3
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia.
4
National Institute for Health and Medical Research (INSERM), UMR 1166 ICAN, Paris F-75013, France; Sorbonne University, Paris F-75013, France; AP-HP, Groupe hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: anatol.kontush@upmc.fr.

Abstract

AIMS:

Human plasma lipoproteins are known to contain various glycan structures whose composition and functional importance are starting to be recognized. We assessed N-glycosylation of human plasma HDL and LDL and the role of their glycomes in cellular cholesterol metabolism.

METHODS:

N-glycomic profiles of native and neuraminidase-treated HDL and LDL were obtained using HILIC-UHPLC-FLD. Relative abundance of the individual chromatographic peaks was quantitatively expressed as a percentage of total integrated area and N-glycan structures present in each peak were elucidated by MALDI-TOF MS. The capacity of HDL to mediate cellular efflux of cholesterol and the capacity of LDL to induce cellular accumulation of cholesteryl esters were evaluated in THP-1 cells.

RESULTS:

HILIC-UHPLC-FLD analysis of HDL and LDL N-glycans released by PNGase F resulted in 22 and 18 distinct chromatographic peaks, respectively. The majority of N-glycans present in HDL (~70%) and LDL (~60%) were sialylated with one or two sialic acid residues. The most abundant N-glycan structure in both HDL and LDL was a complex type biantennary N-glycan with one sialic acid (A2G2S1). Relative abundances of several N-glycan structures were dramatically altered by the neuraminidase treatment, which selectively removed sialic acid residues. Native HDL displayed significantly greater efficacy in removing cellular cholesterol from THP-1 cells as compared to desialylated HDL (p < 0.05). Cellular accumulation of cholesteryl esters in THP-1 cells was significantly higher after incubations with desialylated LDL particles as compared to native LDL (p < 0.05).

CONCLUSIONS:

N-glycome of human plasma lipoproteins reveals a high level of diversity, which directly impacts functional properties of the lipoproteins.

KEYWORDS:

Cholesterol accumulation; Cholesterol efflux; Glycome; High-density lipoprotein; Low-density lipoprotein; Sialic acid

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