Protein carbamylation renders high-density lipoprotein dysfunctional

Antioxid Redox Signal. 2011 Jun 15;14(12):2337-46. doi: 10.1089/ars.2010.3640. Epub 2011 Mar 28.


Carbamylation of proteins through reactive cyanate has been demonstrated to predict an increased cardiovascular risk. Cyanate is formed in vivo by breakdown of urea and at sites of inflammation by the phagocyte protein myeloperoxidase. Because myeloperoxidase (MPO) associates with high-density lipoprotein (HDL) in human atherosclerotic intima, we examined in the present study whether cyanate specifically targets HDL. Mass spectrometry analysis revealed that protein carbamylation is a major posttranslational modification of HDL. The carbamyllysine content of lesion-derived HDL was more than 20-fold higher in comparison with 3-chlorotyrosine levels, a specific oxidation product of MPO. Notably, the carbamyllysine content of lesion-derived HDL was five- to eightfold higher when compared with lesion-derived low-density lipoprotein (LDL) or total lesion protein and increased with lesion severity. The carbamyllysine content of HDL, but not of LDL, correlated with levels of 3-chlorotyrosine, suggesting that MPO mediated carbamylation in the vessel wall. Remarkably, one carbamyllysine residue per HDL-associated apolipoprotein A-I was sufficient to induce cholesterol accumulation and lipid-droplet formation in macrophages through a pathway requiring the HDL-receptor scavenger receptor class B, type I. The present results raise the possibility that HDL carbamylation contributes to foam cell formation in atherosclerotic lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-I / chemistry
  • Apolipoprotein A-I / metabolism
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • CD36 Antigens / metabolism
  • Cells, Cultured
  • Cholesterol / metabolism
  • Cyanates / chemistry
  • Cyanates / metabolism
  • Humans
  • Lipoproteins, HDL / chemistry*
  • Lipoproteins, HDL / metabolism*
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mass Spectrometry
  • Middle Aged
  • Oxidation-Reduction
  • Peroxidase / metabolism
  • Protein Processing, Post-Translational*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Apolipoprotein A-I
  • CD36 Antigens
  • Cyanates
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Tyrosine
  • Cholesterol
  • Peroxidase
  • 3-chlorotyrosine