BINDING AND UPTAKE OF CHYLOMICRON REMNANTS BY CULTURED ARTERIAL SMOOTH-MUSCLE CELLS FROM NORMAL AND WATANABE-HERITABLE-HYPERLIPIDEMIC RABBITS

Chylomicron remnants (RM's) may be involved in atherogenesis because t hey can be delivered to the subendothelial space of arterial vessels a nd serve as substrate for arterial cells. A number of proteins may bin d RM's, however, the quantitative significance of these is not establi shed. The aim of this study was to identify the primary RM binding sit e of arterial smooth muscle cells (SMC's). At 4 degrees C, SMC's displ ayed saturable high affinity binding of RM's. In receptor competition studies, LDL inhibited binding of RM's by almost 60% suggesting involv ement of the apolipoprotein B-100/E receptor. Unlabeled RM's were more effective with an EC50 significantly less than for unlabeled LDL. Fur thermore, at 37 degrees C RM uptake was three times greater than LDL, consistent with greater affinity of the apolipoprotein B-100/E recepto r for lipoproteins containing apolipoprotein E. In SMC's from homozygo te Watanabe heritable hyperlipidemic (WHHL) rabbits, the binding and d egradation of chylomicron remnants was severely impaired. SMC's from c ross-bred WHHL rabbits exhibited levels of binding and degradation int ermediate between homozygote WHHL rabbits and controls, We confirmed t hat the apolipoprotein B-100/E receptor is the primary mechanism by wh ich arterial smooth muscle cells bind and degrade RM's using a polyclo nal antibody which specifically recognises the receptor. In the presen ce of the antibody, RM binding and degradation were inhibited by 90%.