Molecular processing of HDL by the liver during reverse cholesterol transport

[35S)-labelled HDL was prepared from the chyle of rats after feeding [35S)methionine/cysteine. It was added to the perfusate of isolated rat spleens, pre-labelled with [3H)cholesterol and perfused simultaneously with a rat liver. This system allowed the complete process of reverse cholesterol transport to take place while the uptake of individual HDL apolipoproteins and cholesterol by the liver was studied. In 3 h, uptake of apo C, A-IV and E was 24-59% whereas the uptake of apo A-I was negligible. 42% of the [3H)cholesterol entering the perfusate was taken up by the liver with 16% of the HDL cholesteryl ester mass. The results indicate that hepatic uptake of HDL cholesterol and cholesteryl ester is accompanied by some apolipoprotein uptake but not apo A-I. The apo A-I containing HDL particle is released back into the perfusate where it can return to extrahepatic tissues to take up more cholesterol. Further experiments in whole rats showed that human apo A-I (60 mg), when administered to rats i.v. with the [35S)HDL, displaced [35S) into the d > 1.250 density fraction of plasma. This trebled the apparent uptake of unassociated apo A-I into the kidney supporting the hypothesis that the kidney is the organ of destruction of apo A-I.