Elsevier

Kidney International

Volume 88, Issue 3, September 2015, Pages 474-478
Kidney International

Mini Review
Protein carbamylation and cardiovascular disease

https://doi.org/10.1038/ki.2015.166Get rights and content
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Carbamylation constitutes a posttranslational modification of proteins or amino acids and results from different pathways in vivo. First is the non-enzymatic reaction between isocyanic acid, a decomposition product of urea, and either the N-terminus or the ε-amino group of lysine residues. Isocyanic acid levels, while low in vivo, are in equilibrium with urea and are thus increased in chronic and end-stage renal diseases. An alternative pathway involves the leukocyte heme protein myeloperoxidase, which catalyzes the oxidation of thiocyanate in the presence of hydrogen peroxide, producing isocyanate at inflammation sites. Notably, plasma thiocyanate levels are increased in smokers, and leukocyte-driven protein carbamylation occurs both within human and animal atherosclerotic plaques, as well as on plasma proteins. Protein carbamylation is considered a hallmark of molecular aging and is implicated in many pathological conditions. Recently, it has been shown that carbamylated low-density lipoprotein (LDL) induces endothelial dysfunction via lectin-like-oxidized LDL receptor-1 activation and increased reactive oxygen species production, leading to endothelial nitric oxide synthase uncoupling. Moreover, carbamylated LDL harbors atherogenic activities, including both binding to macrophage scavenger receptors inducing cholesterol accumulation and foam-cell formation, as well as promoting vascular smooth muscle proliferation. In contrast, high-density lipoprotein loses its anti-apoptotic activity after carbamylation, contributing to endothelial cell death. In addition to involvement in atherogenesis, protein carbamylation levels have emerged as a particularly strong predictor of both prevalent and incident cardiovascular disease risk. Recent studies also suggest that protein carbamylation may serve as a potential therapeutic target for the prevention of atherosclerotic heart disease.

Keywords

inflammation
uremia
vascular calcification

Cited by (0)

SLH is named as the co-inventor on issued and pending patents held by the Cleveland Clinic relating to cardiovascular diagnostics and/or therapeutics; he is also paid as a consultant for the following companies: Cleveland Heart Laboratory, Esperion, Liposcience, and Procter & Gamble; and has received research funds from the Cleveland Heart Laboratory, Liposcience, Procter & Gamble, and Takeda. SLH reports having the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics and/or therapeutics from Cleveland Heart Laboratory, Siemens, Esperion, and Frantz Biomarkers, LLC. The remaining authors declare no conflict of interest.