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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

El-Gamal, D; Rao, SP; Holzer, M; Hallström, S; Haybaeck, J; Gauster, M; Wadsack, C; Kozina, A; Frank, S; Schicho, R; Schuligoi, R; Heinemann, A; Marsche, G.
The urea decomposition product cyanate promotes endothelial dysfunction.
Kidney Int. 2014; 86(5):923-931 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
El-Gamal Dalia
Frank Saša
Gauster Martin
Hallström Seth
Haybäck Johannes
Heinemann Akos
Holzer Michael
Kirsch Andrijana
Marsche Gunther
Schicho Rudolf
Schuligoi Rufina
Wadsack Christian
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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.

Find related publications in this database (Keywords)
cyanate
endothelial nitric oxide synthase
plasminogen activator inhibitor-1
renal disease
tissue factor
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