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• W1993227310 abstract "We have previously developed triantennary galactosides [TG(4Å)C and TG(20Å)C] that lower cholesterol levels by inducing liver uptake of lipoproteins via galactose-recognizing hepatic receptors. In this study, we have investigated whether this strategy could also be applied to reduce elevated serum levels of the atherogenic lipoprotein(a) [Lp(a)]. Both TG(4Å)C and TG(20Å)C could be incorporated into Lp(a). Incorporation of these glycolipids induced a rapid clearance of Lp(a). Concomitantly, the hepatic uptake of 125 I-Lp(a) was enhanced from 4±1% to 80±4% of the injected dose for TG(4Å)C ( P <.0001) and to 17±4% of the injected dose for TG(20Å)C ( P <.006). TG(4Å)C was apparently more effective in accelerating the serum decay of 125 I-Lp(a), which may be caused by the higher hydrophobicity of this glycolipid relative to TG(20Å)C. The TG(4Å)C- and TG(20Å)C-induced stimulation of the serum decay and liver uptake of 125 I-Lp(a) could be significantly inhibited (>85%) by preinjection of N -acetyl-galactosamine (150 mg), indicating that galactose-recognizing receptors are involved in the liver uptake of the glycolipid/Lp(a) complexes. The TG(4Å)C-induced liver uptake of 125 I-Lp(a) could be ascribed mainly to Kupffer cells (76±7%), whereas the parenchymal liver cell was the major site for liver uptake of TG(20Å)C-laden 125 I-Lp(a) (55±12%). In conclusion, both TG(4Å)C and TG(20Å)C stimulate the catabolism of 125 I-Lp(a) by enhancing hepatic uptake. Because endocytosis of the substrate via galactose-recognizing receptors on Kupffer and parenchymal liver cells is followed by lysosomal degradation, we anticipate that both approaches for Lp(a) targeting may prove valuable as therapeutic modalities for lowering atherogenic levels of Lp(a)." @default.
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• W1993227310 date "1996-12-01" @default.
• W1993227310 modified "2023-10-18" @default.
• W1993227310 title "Induction of Hepatic Uptake of Lipoprotein(a) by Cholesterol-Derivatized Cluster Galactosides" @default.
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• W1993227310 doi "https://doi.org/10.1161/01.atv.16.12.1552" @default.
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