Proteomic and lipidomic analyses of paraoxonase defined high density lipoprotein particles: Association of paraoxonase with the anti-coagulant, protein S

Proteomics Clin Appl. 2016 Mar;10(3):230-8. doi: 10.1002/prca.201500062. Epub 2015 Dec 8.


Purpose: Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction.

Experimental design: Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared.

Results: Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p < 0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p < 0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p < 0.0001), and alpha2 macroglobulin (p < 0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity.

Conclusions and clinical relevance: The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti-atherosclerotic potential.

Keywords: Apolipoprotein; Atherosclerosis; Coagulation; HDL; Lipidomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / metabolism*
  • Aryldialkylphosphatase / metabolism*
  • Humans
  • Immunosorbent Techniques
  • Lipoproteins, HDL / analysis*
  • Lipoproteins, HDL / metabolism
  • Particle Size
  • Protein S / metabolism*
  • Proteomics*


  • Anticoagulants
  • Lipoproteins, HDL
  • Protein S
  • Aryldialkylphosphatase
  • PON1 protein, human