Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.

Takahashi, Sadao; Kawarabayasi, Yutaka; Nakai, Tsuguhiko; Sakai, Juro; Yamamoto, Tokuo

doi:10.1073/pnas.89.19.9252

Cited by 504 publications

(362 citation statements)

References 22 publications

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“…A cDNA for VLDL receptor was cloned by Takahashi et al 25 Although the mature VLDL receptor has a striking homology to the LDL receptor, the two receptors have distinct ligand specificities. The VLDL receptor binds apoE-containing lipoprotein, whereas the LDL receptor binds both apoE-and apoB-100-containing lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

Ishibashi

Yokoyama

Shindo

et al. 1994

Arterioscler Thromb

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The mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) lowers plasma cholesterol levels is not well understood. We tested recombinant human GM-CSF (rhGM-CSF) on plasma cholesterol and triglycerides in rabbits and attempted to determine the mechanisms of the cholesterol-lowering effect. rhGM-CSF (20 /ig • kg" 1 • d" 1 ) was administered to normal and cholesterol-fed rabbits for 2 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for 1 week. The administration of rhGM-CSF markedly lowered cholesterol and triglycerides, an effect that persisted in normal and cholesterol-fed rabbits even after termination of treatment. The cholesterol-lowering effect of rhGM-CSF was also observed in WHHL rabbits. rhGM-CSF was capable of stimulating granulocyte-macrophage colony formation in vitro in rabbits with an effect comparable to that H uman granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of myeloid and monocytic lineages in vitro and in vivo. 1 -2 This substance has been used clinically to treat patients with hematologic and oncologic disorders. 3 ' 4 Besides the effects of GM-CSF on hematopoietic cells, various other actions unrelated to hematopoiesis have been reported, 5 including decreases in plasma cholesterol levels in patients who were receiving human GM-CSF for hematologic disorders. 68 These observations suggest that this molecule might play an important role in lipid metabolism.Another molecule, macrophage colony-stimulating factor (M-CSF), reduces the levels of cholesterol in humans and rabbits in vivo. 911 The mechanisms by which M-CSF lowers plasma cholesterol levels have A preliminary report of this work was presented at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993 (Circulation. 1993 been extensively studied. 10 -1214 The levels of mRNA for low-density lipoprotein (LDL) receptor are increased in spleen and bone marrow cells of normal rabbits, but the levels in liver are not changed after M-CSF treatment. 10 M-CSF stimulates the secretion of lipoprotein lipase and apolipoprotein (apo) E from macrophages 12 and also promotes the uptake and degradation of acetylated LDL, cholesterol esterification, and cholesterol efflux in macrophages. 13 M-CSF also increases net hydrolysis of cholesteryl ester in monocyte-derived macrophages. 14 Both GM-CSF and M-CSF enhance the proliferation and maturation of monocyte/macrophage lineage and have a wide variety of biological effects on various types of cells. 2 -5 -15 To test the hypothesis that the modes of actions of the two molecules on plasma lipid content might be mediated by pathways other than activating macrophages, we administered recombinant human GM-CSF (rhGM-CSF) to normal, cholesterol-fed, and Watanabe heritable hyperlipidemic (WHHL) rabbits to analyze the effect of GM-CSF on the metabolism of lipoproteins. In this article we describe a dramatic decrease in plasma cholesterol and fat levels in rabbits treated with ...

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Section: Discussionmentioning

confidence: 99%

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

Ishibashi

Yokoyama

Shindo

et al. 1994

Arterioscler Thromb

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“…Plasmids encoding the human VLDL receptor (ph-VLR2) or pSV2-neo, which contains the neomycin resistance gene, were transfected to ldlA-7 cells (mutant Chinese hamster ovary cells that lack LDL receptors) which was kindly provided by Dr. Monty Krieger (Department of Biology, Massachusetts Institute of Technology, Cambridge, MA) using lipofectin as described previously [1][2][3]9,12]. Positive cell clones for the human VLDL receptor were designated VLDL-R cells.…”

Section: Isolation Of Transfected Cellsmentioning

confidence: 99%

“…The VLDL receptor has been identified by the cloning of a cDNA from a rabbit heart cDNA library [1]. The amino acid sequence of the VLDL receptor has a striking homology to the low density lipoprotein (LDL) receptor.…”

Section: Introductionmentioning

confidence: 99%

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Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

et al. 1996

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“…[17][18][19][20][21] In lipoprotein metabolism, apoE plays a major role in facilitating the cellular uptake of low density lipoproteins (VLDL) and chylomicron remnants by serving as a ligand on lipoprotein particles for the VLDL receptor and the putative remnant receptor. [22][23][24][25][26][27] In humans, apoE is one of two known ligands for the low density lipoprotein (LDL) receptor. 28 Type III hyperlipoproteinemia and atherosclerotic coronary heart diseases have been found to be associated with genetic variation of apolipoprotein E resulting in defective receptor binding.…”

Section: Introductionmentioning

confidence: 99%

A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E

Cioffi¹,

Sturtz²,

Wittmer³

et al. 1999

Gene Ther

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A major focus in gene therapy has been the use of recomand lesions at a young age. After transplantation of the binant viruses to deliver genes in vivo. Although this apoE secreting Pro 175 endothelial cells into apoEapproach shows much promise, there are many safety deficient mice, serum cholesterol levels were measured at concerns associated with the use of viral materials in the 2 week intervals. During the 3 months after the initiation of treatment of human diseases. Our alternative cell-based these experiments, levels of cholesterol in the animals havgene therapy approach utilizes endothelial cells (Pro 175) ing received the apoE secreting endothelial cells were statisolated from the murine embryonic yolk sac. These endoistically lower compared with the levels of age-matched thelial cells were evaluated for their potential use in gene controls having received non-secreting endothelial cells. therapy as a gene delivery platform. As a test model, we Concomitant with cholesterol reduction, atherosclerotic used these cells to deliver apolipoprotein E (apoE) in the aortic plaques were noticeably reduced in the experimental murine apoE knockout atherosclerosis model. The lack of apoE+ animals. These results highlight the potential of apoE protein in these animals results in high levels of these unique endothelial cells as an efficient delivery serum cholesterol and formation of severe aortic plaques platform for somatic gene therapy.

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Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.

Cited by 504 publications

References 22 publications

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E

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