Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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
Doi: 10.1038/ki.2014.218
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Web of Science
PubMed
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- Leading authors Med Uni Graz
- El-Gamal Dalia
- Marsche Gunther
- Co-authors Med Uni Graz
- Frank Sasa
- Gauster Martin
- Hallström Seth
- Haybäck Johannes
- Heinemann Akos
- Holzer Michael
- Kirsch Andrijana
- 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 (using NLM MeSH Indexing)
- Administration, Inhalation -
- Animals -
- Aorta - drug effects
- Aorta - metabolism
- Aorta - physiopathology
- Cells, Cultured -
- Citrulline - analogs & derivatives
- Citrulline - metabolism
- Cyanates - administration & dosage
- Cyanates - pharmacology
- Dose-Response Relationship, Drug -
- Endothelial Cells - drug effects
- Endothelial Cells - metabolism
- Endothelium, Vascular - drug effects
- Endothelium, Vascular - metabolism
- Endothelium, Vascular - physiopathology
- Humans -
- Male -
- Mice, Inbred C57BL -
- Nitric Oxide Synthase Type III - genetics
- Nitric Oxide Synthase Type III - metabolism
- Phenotype -
- Plasminogen Activator Inhibitor 1 - genetics
- Plasminogen Activator Inhibitor 1 - metabolism
- Protein Processing, Post-Translational -
- RNA, Messenger - metabolism
- Thromboplastin - metabolism
- Time Factors -
- Vasodilation - drug effects
- Vasodilator Agents - pharmacology
- Find related publications in this database (Keywords)
- cyanate
- endothelial nitric oxide synthase
- plasminogen activator inhibitor-1
- renal disease
- tissue factor