title: The very low density lipoprotein receptor mediates the cellular catabolism of lipoprotein lipase and urokinase-plasminogen activator inhibitor type I complexes.
abstract: 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 experiments using an anti-VLDL receptor IgG detected the VLDL receptor in detergent extracts of human aortic endothelial cells, human umbilical vein endothelial cells, and human aortic smooth muscle cells. To gain insight into the role of the VLDL receptor in the vascular endothelium, its ligand binding properties were further characterized. In vitro binding experiments documented that lipoprotein lipase (LpL), a key enzyme 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 receptor 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 fibroblast cell line deficient in the VLDL receptor and the LDL receptor-related protein, another endocytic receptor known to bind LpL and uPA.PAI-1 complexes. Infected fibroblasts that express the VLDL receptor mediate the cellular internalization of 125I-labeled LpL and uPA.PAI-1 complexes, leading to their degradation. Non-infected fibroblasts or fibroblasts infected with the lacZ gene did not internalize these ligands. These studies confirm that the VLDL receptor binds to and mediates the catabolism of LpL and uPA.PAI-1 complexes. Thus, the VLDL receptor may play a unique role on the vascular endothelium in lipoprotein catabolism by regulating levels of LpL and in the regulation of fibrinolysis by facilitating the removal of urokinase complexed with its inhibitor.
authors.affiliation: Holland Laboratory, Department of Biochemistry, American Red Cross, Rockville, Maryland 20855, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Argraves
authors.forename: F D
authors.initials: FD
authors.lastname: Battey
authors.forename: C D
authors.initials: CD
authors.lastname: MacCalman
authors.forename: K R
authors.initials: KR
authors.lastname: McCrae
authors.forename: M
authors.initials: M
authors.lastname: Gåfvels
authors.forename: K F
authors.initials: KF
authors.lastname: Kozarsky
authors.forename: D A
authors.initials: DA
authors.lastname: Chappell
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
authors.forename: D K
authors.initials: DK
authors.lastname: Strickland
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D001011:Aorta / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D026563:LDL-Receptor Related Protein-Associated Protein; D008071:Lipoprotein Lipase / Q000302:isolation & purification / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011973:Receptors, LDL / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014471:Umbilical Veins; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D006023:Glycoproteins; D026563:LDL-Receptor Related Protein-Associated Protein; D017395:Plasminogen Activator Inhibitor 1; D011973:Receptors, LDL; D011994:Recombinant Proteins; C036053:VLDL receptor; D008071:Lipoprotein Lipase; D014568:Urokinase-Type Plasminogen Activator