The involvement of the low density lipoprotein receptor-related protein (LRP) in chylomicron remnant (CR) catabolism was investigated. Ligand blot analyses demonstrated that beta-very low density lipoproteins (beta-VLDL) incubated with apolipoprotein E (beta-VLDL+E) bound to the LRP and low density lipoprotein receptors, whereas active (receptor-binding) alpha-2-macroglobulin (alpha-2M) bound only to LRP partially purified from rat liver membranes. Iodinated-beta-VLDL + E and active alpha-2M showed high affinity binding to the LRP/alpha-2M receptor of low density lipoprotein receptor-negative fibroblasts. The binding and degradation of radiolabeled alpha-2M by these cells were partially inhibited by beta-VLDL+E. Furthermore, alpha-2M interfered with the internalization of beta-VLDL+E and subsequent induction in the cholesterol esterification by these cells. These studies suggested that remnant lipoproteins and active alpha-2M compete for binding to the LRP/alpha-2M receptor. Next, we examined whether the LRP/alpha-2M receptor plays a role, in the presence of low density lipoprotein receptors, in the in vivo catabolism of CR in mice. In vivo studies demonstrated that the unlabeled active, but not the native, alpha-2M partially inhibited the plasma clearance and hepatic uptake of radiolabeled CR or apoE-enriched radiolabeled CR. Likewise, apoE-enriched CR retarded the plasma clearance and hepatic uptake of radiolabeled active alpha-2M. These studies provide physiological evidence that the LRP/alpha-2M receptor may function as a CR receptor that removes CR from the plasma.
Última actualización: 21/10/2016