Abstract 13434: Lp(a) is a Novel Ligand for Scavenger Receptor-B1
Background: Scavenger receptor class B type 1 (SCARB1 or SR-B1), is a multi-ligand receptor, which binds a variety of lipoproteins, including high density lipoprotein (HDL) and low density (LDL), but lipoprotein(a), Lp(a), an pro-atherogenic LDL-like lipoprotein, has not been investigated as a possible ligand. In this study, we test the hypothesis that SCARB1 binds Lp(a) and mediates cellular uptake of cholesteryl ester from Lp(a).
Methods and Results: A HEK 293 cell line stably transfected with SCARB1 showed high affinity specific binding of 125I labeled Lp(a) with a Kd of approximately 32 nM (26 µg/ml). Under confocal microscopy, the cells transfected with SCARB1 showed binding and endocytosis of both protein and lipid of doubly labeled fluorescent Lp(a). In a time course study, 293 cells transfected with or without SCARB1 were incubated with dual-labeled Lp(a) (3H-CE-[125I]-Lp(a), which contained a non-hydrolyzable analog of cholesteryl ester. An increase in 3H-CE-[125I] binding was observed in SCARB1 (+) 293 cells, but not in control cells . The level of 125I counts associated with the cells reached a plateau at 2 hours. However, the level of 3H was increased more than 2.5-fold after 2 hours of incubation and continued to increase to a level 10-fold above control after 8 hours, indicating that the receptor selectively mediates intracellular lipid uptake. When a low concentration of [125I]-Lp(a) (10 µg/ml) was used, no Lp(a) degradation was observed. With higher doses (30 µg/ml) of Lp(a), the cells transfected with SCARB1 were found to have increased protein degradation . Western blotting detected full length Lp(a) but no apoB in cellular lysates , and the media of SCARB1(+) cells contained a decreased amount of apoB suggesting possible degradation of apoB.
Conclusion: We demonstrate that Lp(a) is a novel ligand for SCARB1. SCARB1 binds and endocytoses whole Lp(a) particles, promotes uptake of cholesteryl ester from Lp(a) and partially degrades Lp(a) protein.
- © 2011 by American Heart Association, Inc.