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- Title
Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.
- Authors
Asci, Gulay; Basci, Ali; Shah, Sudhir V.; Basnakian, Alexei; Toz, Huseyin; Ozkahya, Mehmet; Duman, Soner; Ok, Ercan
- Abstract
Aim: 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. Conclusion: The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.
- Subjects
ATHEROSCLEROSIS; HEMODIALYSIS patients; KIDNEY diseases; CARCINOGENESIS; VASCULAR smooth muscle; LACTATE dehydrogenase
- Publication
Nephrology, 2008, Vol 13, Issue 6, p480
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/j.1440-1797.2008.00948.x