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

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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cholesterol / metabolism
  • Cholesterol Esters / metabolism
  • Glycosylation
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / chemistry
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / metabolism*
  • N-Acetylneuraminic Acid / analysis
  • N-Acetylneuraminic Acid / metabolism
  • Polysaccharides / analysis
  • Polysaccharides / metabolism


  • Cholesterol Esters
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Polysaccharides
  • Cholesterol
  • N-Acetylneuraminic Acid