Cholesteryl esters from oxidized low-density lipoproteins are in vivo rapidly hydrolyzed in rat kupffer cells and transported to liver parenchymal cells and bile
✍ Scribed by Moniek N. Pieters; Sebastiaan Esbach; Donald Schouten; Adriaan Brouwer; Dick L. Knook; Theo J. C. Van Berkel
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 909 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Human low-density lipoprotein was labeled in its cholesteryl ester moiety with [SHlcholesteryl oleate or [SHlcholesteryl oleoyl ether and oxidized by exposure to 10 pmoW of cupric sulfate. The in uiuo metabolism of cholesteryl esters of oxidized low-density lipoprotein W ~E J determined after injection into rats. When oxidized low-density lipoprotein was labeled with [SHlcholeeteryl oleoyl ether, a nonhydrolyzable analog of cholesteryl oleate, Kupffer cells contributed to 56.1% f 4.1% of the total liver uptake 10 min after injection. When [SHlcholesteryl 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-associated radioactivity declined to 32% of the maximal uptake value. In serum, the highest specHc resecreted [5Hlcholesteryl (esters) were asso- ciated with the serum high-density lipoprotein fraction, suggesting a role for high-density lipoprotein as an in v i m cholesterol acceptor. The kinetics of biliary secretion were studied in rats equipped with catheters in the bile duct, duodenum and heart. One hour after injection of [8Hlcholeeteryl oleate-labeled oxidized low-density lipoprotein, 4.16% f 0.67% of the injected dose was secreted in the bile, mainly as bile acids. Six hours after injection, this value was 19.2% f 1.2%. These values are three times higher than those for injected [~lcholesteryl oleate-labeled acetylated lowdensity lipoprotein, which is initially mainly taken up by liver endothelial cells. The rapid processing of cholesteryl esters derived from oxidized low-density lipoprotein to bile acids indicates that Kupffer cells form an efficient protection system against the athero-