THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR MEDIATES THE CELLULAR CATABOLISM OF LIPOPROTEIN-LIPASE AND UROKINASE-PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I COMPLEXES

The very low density Lipoprotein (VLDL) receptor binds apolipoprotein E-rich lipoproteins as well as the 39-kDa receptor-associated protein (RAP). Ligand blotting experiments using RAP and immunoblotting experi ments using an anti-VLDL receptor IgG detected the VLDL receptor in de tergent extracts of human aortic endothelial cells, human umbilical ve in endothelial cells, and human aortic smooth muscle cells. To gain in sight into the role of the VLDL receptor in the vascular endothelium, its ligand binding properties were further characterized. In vitro bin ding experiments documented that lipoprotein lipase (LpL), a key enzym e in lipoprotein catabolism, binds with high affinity to purified VLDL receptor. In addition, urokinase complexed with plasminogen activator -inhibitor type I (uPA . PAI-1) also bound to the purified VLDL recept or with high affinity. To assess the capacity of the VLDL receptor to mediate the cellular internalization of ligands, an adenoviral vector was used to introduce the VLDL receptor gene into a murine embryonic f ibroblast cell line deficient in the VLDL receptor and the LDL recepto r-related protein, another endocytic receptor known to bind LpL and uP A . PAI-1 complexes. Infected fibroblasts that express the VLDL recept or mediate the cellular internalization of I-125-labeled LpL and uPA . PAI-1 complexes, leading to their degradation. Non-infected fibroblas ts or fibroblasts infected with the lacZ gene did not internalize thes e ligands. These studies confirm that the VLDL receptor binds to and m ediates the catabolism of LpL and uPA . PAI-1 complexes. Thus, the VLD L receptor may play a unique role on the vascular endothelium in lipop rotein catabolism by regulating levels of LpL and in the regulation of fibrinolysis by facilitating the removal of urokinase complexed with its inhibitor.