Myeloperoxidase-derived chlorinating species induce protein carbamylation through decomposition of thiocyanate and urea: novel pathways generating dysfunctional high-density lipoprotein

Antioxid Redox Signal. 2012 Oct 15;17(8):1043-52. doi: 10.1089/ars.2011.4403. Epub 2012 May 8.


Aims: Protein carbamylation through cyanate is considered as playing a causal role in promoting cardiovascular disease. We recently observed that the phagocyte protein myeloperoxidase (MPO) specifically induces high-density lipoprotein (HDL) carbamylation, rather than chlorination, in human atherosclerotic lesions, raising the possibility that MPO-derived chlorinating species are involved in cyanate formation.

Results: Here, we show that MPO-derived chlorinating species rapidly decompose the plasma components thiocyanate (SCN) and urea, thereby promoting (lipo)protein carbamylation. Strikingly, the presence of physiologic concentrations of SCN completely prevented MPO-induced 3-chlorotyrosine formation in HDL. SCN scavenged a 2.5-fold molar excess of hypochlorous acid, promoting HDL carbamylation, but not chlorination. Cyanate significantly impaired (i) HDL's ability to activate lecithin-cholesterol acyltransferase; (ii) the activity of paraoxonase, a major HDL-associated anti-inflammatory enzyme; and (iii) the antioxidative activity of HDL.

Innovation: Here, we report that MPO-derived chlorinating species preferentially induce protein carbamylation-rather than chlorination-in the presence of physiologically relevant SCN concentrations. The carbamylation of HDL results in the loss of its anti-inflammatory and antioxidative activities.

Conclusion: MPO-mediated decomposition of SCN and/or urea might be a relevant mechanism for generating dysfunctional HDL in human disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Chlorine / metabolism*
  • Humans
  • Hypochlorous Acid / chemistry
  • Lipoproteins, HDL / isolation & purification
  • Lipoproteins, HDL / metabolism*
  • Lysine / metabolism
  • Peroxidase / metabolism*
  • Thiocyanates / blood
  • Thiocyanates / chemistry
  • Thiocyanates / metabolism*
  • Urea / blood
  • Urea / chemistry
  • Urea / metabolism*


  • Antioxidants
  • Lipoproteins, HDL
  • Thiocyanates
  • Chlorine
  • Hypochlorous Acid
  • Urea
  • Peroxidase
  • Lysine
  • thiocyanate