Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.
OBJECTIVE
Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC).


METHODS
Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied.


RESULTS
Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis.


CONCLUSIONS
The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.
Department of Internal Medicine, Division of Nephrology, Ege University School of Medicine, Izmir, Turkey. gulayas@hotmail.com
Gulay
G
Asci
Ali
A
Basci
Sudhir V
SV
Shah
Alexei
A
Basnakian
Huseyin
H
Toz
Mehmet
M
Ozkahya
Soner
S
Duman
Ercan
E
Ok
D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000209:etiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000150:complications; D008077:Lipoproteins, LDL / Q000097:blood / Q000633:toxicity*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D016326:Extracellular Matrix Proteins; D008077:Lipoproteins, LDL; D019010:Vascular Cell Adhesion Molecule-1; C039916:carbamyl-LDL; D018799:Intercellular Adhesion Molecule-1