Abstract-Since the molecular identification of the low density lipoprotein receptor (LDLR), an ever increasing number of related proteins have been discovered. These receptors belonging to the LDLR family are thought to play key roles in lipoprotein metabolism in a variety of tissues, including the arterial wall. We have discovered that the expression of a 250-kDa mosaic LDLR-related protein, which we termed LR11 for the presence of 11 LDLR ligand-binding repeats, is markedly induced in smooth muscle cells in the hyperplastic intima of animal models used for the study of atherosclerosis. Here, we demonstrate that the human LR11, when overexpressed in hamster cells, binds and internalizes 39-kDa receptor-associated protein (RAP), an in vitro ligand for all receptors belonging to the LDLR family. Furthermore, LR11 binds the apolipoprotein E (apoE)-rich lipoproteins, ␤-very low density lipoproteins (VLDLs), with a high affinity similar to that of other members, such as the LDLR and VLDL receptor. RAP and ␤-VLDL compete with each other; however, other serum lipoproteins are not able to inhibit their binding. LR11 shows specific binding of apoE-enriched HDL prepared from human cerebrospinal fluid as well as of ␤-VLDL, suggesting that the apoE content of lipoproteins is most likely important for mediating the high-affinity binding to the receptor. LR11-overexpressing cells are able to internalize and degrade the bound ␤-VLDL; these cells also show increased accumulation of cholesteryl esters when incubated with ␤-VLDL. Incubation for 48 hours with ␤-VLDL of LR11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets. Taken together, LR11, a mosaic LDLR family member whose expression in smooth muscle cells is markedly induced in atheroma, has all the properties of a receptor for the endocytosis of lipoproteins, particularly for the incorporation of apoE-rich lipoproteins. Key Words: LDL receptors Ⅲ atherosclerosis Ⅲ smooth muscle cells Ⅲ ␤-VLDL R eceptors belonging to the LDL receptor (LDLR) family are thought to play key roles in lipoprotein metabolism in a variety of tissues, including the arterial wall. [1][2][3][4] Recent extensive histochemical studies have shown that receptors belonging to the LDLR family, as well as scavenger receptors mediating the incorporation of modified lipoproteins such as oxidized LDL, show marked induction of their expression during the formation of atherosclerotic lesions. [5][6][7][8][9] For instance, 1 LDLR family member, the so-called VLDL receptor (VLDLR/LR8), has been shown to be highly expressed in smooth muscle cells (SMCs), macrophages, and endothelial cells in rabbit atherosclerotic lesions. 7-9 Furthermore, VLDLR/LR8 has been shown not to be downregulated during ␤-VLDL-induced foam cell formation in vitro, and overexpression of the receptor in fibroblasts causes excessive lipid droplet accumulation in the transformed cells. 10 We and others have discovered and molecularly characterized a novel, unusually complex, and hi...

Pre-heparin plasma LPL mass is closely associated with intra-abdominal fat distribution, and the measurement of its value gives useful information concerning metabolic disorder.

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