ROLE OF HDL1 IN CHOLESTERYL ESTER UPTAKE IN RATS

It has been suggested that apoE may play a central role in reverse cho lesterol transport in rats. By this hypothesis, cholesteryl esters (CE ) accumulate in high density lipoprotein (HDL) particles, which acquir e apoE at the expense of apoA-I, and the apoE targets them for rapid h epatic uptake. However, the pathway has not been directly assessed in vivo. We directly traced the metabolism of HDL1 cholesteryl esters in rats. To do this, rat HDL, was labeled in its apoE and CE moieties, an d HDL2 free of apoE was labeled in its apoA-I and CE moieties; C-14 or H-3-labeled cholesteryl-oleyl ether traced the CE moieties and the I- 125 or I-131-labeled N-methyltyramine cellobiose (NMTC) ligand traced the apolipoprotein moietics. The labeled HDLs were injected, plasma de cays were followed, and tissues were examined after 24 h. ApoE tracer decayed from plasma 2.4-times faster than HDL1 CE and 1.8-times faster than HDL2 CE. HDL1 CE decayed significantly more slowly than HDL2 CE (0.75-times). As expected, hepatic uptake of HDL2 CE was mostly by sel ective (indirect) uptake. However, hepatic uptake of HDL1 CE was at a fractional rate significantly lower than that of HDL2 CE (0.69-times), even though the uptake of apoE was much higher. The plasma decay of H DL1 apoE evidently reflects in large part the uptake of apoE after tra nsfer to other fractions, and it over-estimates the clearance of HDL1 CE. Selective uptake plays the major role in hepatic HDL CE uptake in rats.