The urea decomposition product cyanate promotes endothelial dysfunction

Dalia A ElGamal, Shailaja P. Rao, Michael Holzer, Seth Hallström, Johannes Haybaeck, Martin Gauster, Christian Wadsack, Andrijana Kozina, Saša Frank, Rudolf Schicho, Rufina Schuligoi, Akos Heinemann, Gunther Marsche

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The dramatic cardiovascular mortality of patients with chronic kidney disease is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase, and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate, promoting protein carbamylation at levels observed in uremic patients, attenuated arterial vasorelaxation of aortic rings in response to acetylcholine without affecting the sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. Thus, cyanate compromises endothelial functionality in vitro and in vivo. This may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease.

Original languageEnglish (US)
Pages (from-to)923-931
Number of pages9
JournalKidney International
Volume86
Issue number5
DOIs
StatePublished - Nov 5 2014

Fingerprint

Cyanates
Urea
Chronic Renal Insufficiency
Nitric Oxide Synthase Type III
Plasminogen Activator Inhibitor 1
Thromboplastin
Tissue Plasminogen Activator
Endothelial Cells
Replication Protein C
Nitroprusside
Vasodilation
Acetylcholine
Aorta
Epitopes
Coronary Vessels
Nitric Oxide
Cardiovascular Diseases
Mortality

Keywords

  • cyanate
  • endothelial nitric oxide synthase
  • plasminogen activator inhibitor-1
  • renal disease
  • tissue factor

ASJC Scopus subject areas

  • Nephrology

Cite this

ElGamal, D. A., Rao, S. P., Holzer, M., Hallström, S., Haybaeck, J., Gauster, M., ... Marsche, G. (2014). The urea decomposition product cyanate promotes endothelial dysfunction. Kidney International, 86(5), 923-931. https://doi.org/10.1038/ki.2014.218

The urea decomposition product cyanate promotes endothelial dysfunction. / ElGamal, Dalia A; Rao, Shailaja P.; Holzer, Michael; Hallström, Seth; Haybaeck, Johannes; Gauster, Martin; Wadsack, Christian; Kozina, Andrijana; Frank, Saša; Schicho, Rudolf; Schuligoi, Rufina; Heinemann, Akos; Marsche, Gunther.

In: Kidney International, Vol. 86, No. 5, 05.11.2014, p. 923-931.

Research output: Contribution to journalArticle

ElGamal, DA, Rao, SP, Holzer, M, Hallström, S, Haybaeck, J, Gauster, M, Wadsack, C, Kozina, A, Frank, S, Schicho, R, Schuligoi, R, Heinemann, A & Marsche, G 2014, 'The urea decomposition product cyanate promotes endothelial dysfunction', Kidney International, vol. 86, no. 5, pp. 923-931. https://doi.org/10.1038/ki.2014.218
ElGamal DA, Rao SP, Holzer M, Hallström S, Haybaeck J, Gauster M et al. The urea decomposition product cyanate promotes endothelial dysfunction. Kidney International. 2014 Nov 5;86(5):923-931. https://doi.org/10.1038/ki.2014.218
ElGamal, Dalia A ; Rao, Shailaja P. ; Holzer, Michael ; Hallström, Seth ; Haybaeck, Johannes ; Gauster, Martin ; Wadsack, Christian ; Kozina, Andrijana ; Frank, Saša ; Schicho, Rudolf ; Schuligoi, Rufina ; Heinemann, Akos ; Marsche, Gunther. / The urea decomposition product cyanate promotes endothelial dysfunction. In: Kidney International. 2014 ; Vol. 86, No. 5. pp. 923-931.
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