Novel mechanisms in accelerated atherosclerosis in kidney disease.
OBJECTIVE
Urea undergoes a spontaneous, nonenzymatic transformation to cyanate, the active part of which is isocyanic acid, which can cause modifications of a variety of proteins in a process called carbamylation. We postulated that, in patients with renal disease, the carbamylation of low-density lipoprotein (LDL) is a nontraditional risk factor for cardiovascular disease, and that elevated urea leads to carbamylated LDL (cLDL), which causes vascular injury and leads to atherosclerosis.


RESULTS
We showed that carbamylated LDL manifests all of the biological effects relevant to atherosclerosis, including endothelial-cell injury, the expression of adhesion molecules, and vascular smooth muscle cell proliferation. We also developed an enzyme-linked immunosorbent assay to measure carbamylated LDL in patients, and showed that cLDL is markedly elevated in dialysis patients.


CONCLUSIONS
Our data indicate that cLDL may be an important nontraditional risk factor for atherosclerosis in patients with kidney disease.
Shah
Sudhir V
SV
Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. shahsudhirv@uams.edu
Apostolov
Eugene O
EO
Ok
Ercan
E
Basnakian
Alexei G
AG
D050197:Atherosclerosis / Q000453:epidemiology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects / Q000633:toxicity; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D014508:Urea / Q000009:adverse effects
D015415:Biomarkers; D008077:Lipoproteins, LDL; C039916:carbamyl-LDL; D014508:Urea