Key Points
- To investigate the mechanism by which cholesterol-rich very low density lipoproteins (VLDL) from Watanabe heritable hyperlipidemic (WHHL) rabbits stimulate cholesteryl ester accumulation in macrophages.
- Incubated mouse peritoneal macrophages with VLDL isolated from homozygous WHHL rabbits or normal control Japanese White rabbits.
- Assayed cholesteryl [14C]oleate synthesis and measured cellular binding, uptake, and lysosomal degradation using 125I-labeled WHHL-VLDL.
- Conducted competition assays using unlabeled WHHL-VLDL, beta-VLDL, LDL, and scavenger receptor competitors (acetyl-LDL, fucoidin, polyinosinic acid, and polyguanylic acid).
- WHHL-VLDL stimulated macrophage cholesteryl [14C]oleate synthesis 124-fold more than control VLDL.
- Uptake and lysosomal degradation of 125I-WHHL-VLDL were mediated by a high-affinity cell-surface receptor inhibited by excess WHHL-VLDL and beta-VLDL, but not by LDL.
- Degradation of WHHL-VLDL was not inhibited by acetyl-LDL or classic scavenger receptor antagonists, indicating an uptake mechanism independent of the acetyl-LDL binding site.
Structured PICO
PPopulationMouse peritoneal macrophages
IInterventionCholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit
CComparatorVLDL from the normal Japanese White rabbit (control-VLDL)
OOutcomeCholesteryl ester synthesis and accumulationsurrogate
Cholesterol-rich VLDL from WHHL rabbits induces marked cholesteryl ester accumulation in macrophages via a high-affinity receptor, suggesting a mechanism for atherosclerosis pathogenesis.