CHOLESTERYL ESTERS FROM OXIDIZED LOW-DENSITY LIPOPROTEINS ARE IN-VIVORAPIDLY HYDROLYZED IN RAT KUPFFER CELLS AND TRANSPORTED TO LIVER PARENCHYMAL-CELLS AND BILE

Citation
Mn. Pieters et al., CHOLESTERYL ESTERS FROM OXIDIZED LOW-DENSITY LIPOPROTEINS ARE IN-VIVORAPIDLY HYDROLYZED IN RAT KUPFFER CELLS AND TRANSPORTED TO LIVER PARENCHYMAL-CELLS AND BILE, Hepatology, 19(6), 1994, pp. 1459-1467
Citations number
33
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
02709139
Volume
19
Issue
6
Year of publication
1994
Pages
1459 - 1467
Database
ISI
SICI code
0270-9139(1994)19:6<1459:CEFOLL>2.0.ZU;2-N
Abstract
Human low-density lipoprotein was labeled in its cholesteryl ester moi ety with [H-3]cholesteryl oleate or [H-3]cholesteryl oleoyl ether and oxidized by exposure to 10 mu mol/L of cupric sulfate. The in vivo met abolism of cholesteryl esters of oxidized low-density lipoprotein was determined after injection into rats. When oxidized low density lipopr otein was labeled with [H-3]cholesteryl oleoyl ether, a nonhydrolyzabI e analog of cholesteryl oleate, Kupffer cells contributed to 55.1% +/- 4.1% of the total liver uptake 10 min after injection. When [H-3]chol esteryl oleate-labeled oxidized low-density lipoprotein was injected, the radiolabeled cholesterol esters were nearly completely hydrolyzed within 1 hr of injection. Within this time, the Kupffer cell-associate d radioactivity declined to 32% of the maximal uptake value. In serum, the highest specific resecreted [H-3]cholesteryl (esters) were associ ated with the serum high-density lipoprotein fraction, suggesting a ro le for high-density lipoprotein as an in vivo cholesterol acceptor. Th e kinetics of biliary secretion were studied in rats equipped with cat heters in the bile duct, duodenum and heart. One hour after injection of [H-3]cholesteryl oleate-labeled oxidized low-density lipoprotein, 4 .15% +/- 0.67% of the injected dose was secreted in the bile, mainly a s bile acids. Six hours after injection, this value was 19.2% +/- 1.2% . These values are three times higher than those for injected [H-3]cho lesteryl oleate-labeled acetylated low-density lipoprotein, which is i nitially mainly taken up by liver endothelial cells. The rapid process ing of cholesteryl esters derived from oxidized low-density lipoprotei n to bile acids indicates that Kupffer cells form an efficient protect ion system against the atherogenic action of oxidized low-density lipo protein in the blood compartment.