title: Cyanate is a novel inducer of endothelial icam-1 expression.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Here, we demonstrate for the first time that cyanate, rather than carbamylated lipoproteins, induces vascular ICAM-1 expression in vivo.
  
  
  CONCLUSIONS
  Collectively, our data raise the possibility that cyanate amplifies vascular inflammation, linking inflammation, smoking, and uremia.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
authors.forename: Dalia
authors.initials: D
authors.lastname: El-Gamal
authors.forename: Michael
authors.initials: M
authors.lastname: Holzer
authors.forename: Martin
authors.initials: M
authors.lastname: Gauster
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schicho
authors.forename: Veronika
authors.initials: V
authors.lastname: Binder
authors.forename: Viktoria
authors.initials: V
authors.lastname: Konya
authors.forename: Christian
authors.initials: C
authors.lastname: Wadsack
authors.forename: Rufina
authors.initials: R
authors.lastname: Schuligoi
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.forename: Gunther
authors.initials: G
authors.lastname: Marsche
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003485:Cyanates / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D051437:Renal Insufficiency / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D003485:Cyanates; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases