Cyanate is a novel inducer of endothelial ICAM-1 expression

Dalia El-Gamal, Michael Holzer, Martin Gauster, Rudolf Schicho, Veronika Binder, Viktoria Konya, Christian Wadsack, Rufina Schuligoi, Akos Heinemann, Gunther Marsche

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24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalAntioxidants and Redox Signaling
Volume16
Issue number2
DOIs
Publication statusPublished - Jan 15 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

El-Gamal, D., Holzer, M., Gauster, M., Schicho, R., Binder, V., Konya, V., ... Marsche, G. (2012). Cyanate is a novel inducer of endothelial ICAM-1 expression. Antioxidants and Redox Signaling, 16(2), 129-137. https://doi.org/10.1089/ars.2011.4090