Metabolism of cholesterol-rich chylomicroms. Mechanism of binding and uptake of cholesteryl esters by the vascular bed of the perfused rat heart

Abstract

The rate of uptake of cholesteryl ester from chylomicrons has been determined with the isolated perfused rat heart and both intact and functionally hepatectomized rats. Uptake was found to be proportional to the cholesteryl ester content of the particles. Transfer of cholesteryl ester to other lipoprotein classes of the plasma was negligible under these conditions, and loss of cholesteryl ester from the medium was associated with quantitative recovery in the vascular bed. The uptake mechanism was nonsaturable and independent of the lipoprotein lipase binding site. Compared with receptor-dependent uptake of low density lipoprotein cholesteryl ester by heart endothelium, the chylomicron pathway appears to provide a major proportion of cholesteryl ester cleared from the plasma. Uptake was initially heparin dependent, and cleared lipid was released by 10 microgram/ml of heparin; however, lipid taken up rapidly became heparin resistant and was then hydrolyzed slowly with production of unesterified fatty acid. These results are discussed in the context of the possible role of cholesterol-rich chylomicron remnant lipoproteins in atherogenesis.