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- Open Access
Urea induces intercellular adhesion molecule-1 expression
BMC Pharmacology volume 11, Article number: A34 (2011)
The dramatically increased cardiovascular risk in patients with chronic renal disease cannot be explained entirely by traditional cardiovascular risk factors. The continuous exposure of renal patients to elevated levels of urea may contribute to increased inflammation and oxidative stress. While urea may not be directly toxic, many molecules can be carbamylated through cyanate, a reactive decomposition product of urea. Cyanate irreversibly transforms lysine to ε-amino-carbamyl lysine. This pathway may be of particular relevance since clinical studies have shown that carbamylated proteins are independent risk factors for the development of coronary artery disease and stroke.
Methods and results
Here we show that urea potently induces intracellular cell adhesion molecule-1 (ICAM-1) expression with subsequently enhanced neutrophil adhesion in human coronary artery endothelial cells. ICAM-1 expression is triggered through a mechanism depending upon activation of the mitogen-activated protein kinase p38 and nuclear factor κB. Interestingly, ICAM-1 expression was not induced when low-molecular weight substances were removed from cell culture medium, ruling out a role of carbamylated (lipo)proteins in ICAM-1 induction. Moreover, in end-stage renal disease patients the extent of plasma protein carbamylation (a marker for cyanate formation) correlated significantly with plasma levels of soluble ICAM-1.
Collectively, our data raise the possibility that urea amplifies vascular inflammation in renal patients.
This work was supported by FWF grants (P21004-B02, P22521-B18 and P22976-B18) and the PhD program MOLMED of the Medical University of Graz.
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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El-Gamal, D., Holzer, M., Binder, V. et al. Urea induces intercellular adhesion molecule-1 expression. BMC Pharmacol 11 (Suppl 2), A34 (2011). https://doi.org/10.1186/1471-2210-11-S2-A34
- Chronic Renal Disease
- Human Coronary Artery
- Neutrophil Adhesion
- Traditional Cardiovascular Risk Factor
- Renal Patient