AIM: Recent work has shown that humans are significantly exposed to isocyanic 
acid/cyanate, which is generated when coal, biomass, or tobacco is burned. In 
vivo, cyanate is formed by the phagocyte protein myeloperoxidase and by 
breakdown of urea. Carbamylation of proteins through cyanate has been 
demonstrated to predict cardiovascular risk and is thought to promote vascular 
dysfunction; however, the underlying mechanisms remain unclear.
RESULTS: Here, we show that cyanate induces intercellular cell adhesion 
molecule-1 (ICAM-1) expression with subsequently enhanced neutrophil adhesion in 
human coronary artery endothelial cells. Cyanate triggers ICAM-1 expression 
through a mechanism depending on activation of the mitogen-activated protein 
kinase p38 and nuclear factor-kappaB. Endothelial ICAM-1 expression was not 
induced when low-molecular-weight substances were removed from cell culture 
medium, thus ruling out a role of carbamylated (lipo)proteins in ICAM-1 
induction. In mice, oral administration of cyanate induced marked endothelial 
ICAM-1 expression in the aorta. Moreover, in patients with end-stage renal 
disease, the extent of plasma protein carbamylation (a marker for cyanate 
exposure) significantly correlated with plasma levels of soluble ICAM-1.
INNOVATION: Here, we demonstrate for the first time that cyanate, rather than 
carbamylated lipoproteins, induces vascular ICAM-1 expression in vivo.
CONCLUSION: Collectively, our data raise the possibility that cyanate amplifies 
vascular inflammation, linking inflammation, smoking, and uremia.