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 they can be delivered to the subendothelial space of arterial vessels and serve as substrate for arterial cells. A number of proteins may bind RM's, however, the quantitative significance of these is not established. The aim of this study was to identify the primary RM binding site of arterial smooth muscle cells (SMC's). At 4 degrees C, SMC's displayed saturable high affinity binding of RM's. In receptor competition studies, LDL inhibited binding of RM's by almost 60% suggesting involvement of the apolipoprotein B100/E receptor. Unlabeled RM's were more effective with an EC50 significantly less than for unlabeled LDL. Furthermore, at 37 degrees C RM uptake was three times greater than LDL, consistent with greater affinity of the apolipoprotein B100/E receptor for lipoproteins containing apolipoprotein E. In SMC's from homozygote Watanabe heritable hyperlipidemic (WHHL) rabbits, the binding and degradation of chylomicron remnants was severely impaired. SMC's from cross-bred WHHL rabbits exhibited levels of binding and degradation intermediate between homozygote WHHL rabbits and controls. We confirmed that the apolipoprotein B100/E receptor is the primary mechanism by which arterial smooth muscle cells bind and degrade RM's using a polyclonal antibody which specifically recognises the receptor. In the presence of the antibody, RM binding and degradation were inhibited by 90%.
Yu
K C
KC
Department of Physiology, University of Western Australia, Nedlands.
Mamo
J C
JC
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D001667:Binding, Competitive; D015153:Blotting, Western; D002478:Cells, Cultured; D002914:Chylomicrons / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D011973:Receptors, LDL / Q000276:immunology / Q000378:metabolism
D002914:Chylomicrons; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL