Abnormal cell-interactive properties of low-density lipoproteins isolated from patients with chronic renal failure.
Patients with renal failure on maintenance hemodialysis have accelerated rate of atherosclerosis. This, and the fact that chemically modified low-density lipoproteins (LDL) have a better capacity than native LDL to stimulate cholesteryl ester accumulation within macrophages in the vessel wall, led us to examine the possibility that some alteration in apo-LDL may take place in chronically uremic patients. We isolated LDL (d = 1.019 - 1.063 g/mL) from 18 patients with chronic renal failure and from 13 normolipidemic controls and compared the interactive properties of the different LDL preparations with cultured fibroblasts. Our results show that "uremic" LDL associates less, is degraded less, and has diminished ability to stimulate cholesteryl ester formation in fibroblasts when compared to normal LDL. LDL carbamylated in vitro showed interactive properties with fibroblasts similar to those of uremic LDL. Uremic LDL was not taken up by scavenger receptors present on rat peritoneal macrophages, similarly to normal LDL. However, the decrease in uptake by fibroblasts of uremic LDL may increase the residence time of these particles within the subendothelial region of the vessel wall, ultimately resulting in increased atherogenicity. Carbamylation of lysine residues of apoB in vivo, abnormal catabolism of LDL due to the absence of functional renal tissue, or triglyceride enrichment of LDL are among the possible explanations for the abnormal properties of uremic LDL.
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051381:Rats; D014511:Uremia / Q000097:blood
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL