Post-translational modification and functional impairment of proteins through 
carbamylation is thought to promote vascular dysfunction during end-stage renal 
disease. Cyanate, a reactive species in equilibrium with urea, carbamylates 
protein lysine residues to form epsilon-carbamyllysine (homocitrulline), 
altering protein structure and function. We now report the discovery of an 
alternative and quantitatively dominant mechanism for cyanate formation and 
protein carbamylation at sites of inflammation and atherosclerotic plaque: 
myeloperoxidase-catalyzed oxidation of thiocyanate, an anion abundant in blood 
whose levels are elevated in smokers. We also show that 
myeloperoxidase-catalyzed lipoprotein carbamylation facilitates multiple 
pro-atherosclerotic activities, including conversion of low-density lipoprotein 
into a ligand for macrophage scavenger receptor A1 recognition, cholesterol 
accumulation and foam-cell formation. In two separate clinical studies (combined 
n = 1,000 subjects), plasma levels of protein-bound homocitrulline independently 
predicted increased risk of coronary artery disease, future myocardial 
infarction, stroke and death. We propose that protein carbamylation is a 
mechanism linking inflammation, smoking, uremia and coronary artery disease 
pathogenesis.