Scavenger receptor-BI is a receptor for lipoprotein(a)

Xiao Ping Yang, Marcelo J. Amar, Boris Vaisman, Alexander V. Bocharov, Tatyana G. Vishnyakova, Lita A. Freeman, Roger J. Kurlander, Amy P. Patterson, Lewis C. Becker, Alan T. Remaley

Research output: Contribution to journalArticle

Abstract

Scavenger receptor class B type I (SR-BI) is a multi-ligand receptor that binds a variety of lipoproteins, including high density lipoprotein (HDL) and low density lipoprotein (LDL), but lipoprotein(a) [Lp(a)] has not been investigated as a possible ligand. Stable cell lines (HEK293 and HeLa) expressing human SR-BI were incubated with protein- or lipid-labeled Lp(a) to investigate SR-BI-dependent Lp(a) cell association. SR-BI expression enhanced the association of both 125I-and Alexa Fluor-labeled protein from Lp(a). By confocal microscopy, SR-BI was also found to promote the internalization of fluorescent lipids (BODIPYcholesteryl ester (CE)- and DiI-labeled) from Lp(a), and by immunocytochemistry the cellular internalization of apolipoprotein(a) and apolipoprotein B. When dual-labeled ( 3H-cholesteryl ether, 125I-protein) Lp(a) was added to cells expressing SR-BI, there was a greater relative increase in lipid uptake over protein, indicating that SR-BI mediates selective lipid uptake from Lp(a). Compared with C57BL/6 control mice, transgenic mice overexpressing human SR-BI in liver were found to have increased plasma clearance of 3H-CE-Lp(a) , whereas mouse scavenger receptor class B type I knockout (Sr-b1-KO) mice had decreased plasma clearance (fractional catabolic rate: 0.63 ± 0.08/day, 1.64 ± 0.62/day, and 4.64 ± 0.40/day for Sr-b1-KO, C57BL/6, and human scavenger receptor class B type I transgenic mice, respectively). We conclude that Lp(a) is a novel ligand for SR-BI and that SR-BI mediates selective uptake of Lp(a)- associated lipids.

Original languageEnglish (US)
Pages (from-to)2450-2457
Number of pages8
JournalJournal of Lipid Research
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2013

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Keywords

  • Apolipoprotein(a)
  • Atherosclerosis
  • Lipoprotein receptors
  • Oxidized lipids
  • Selective uptake

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Yang, X. P., Amar, M. J., Vaisman, B., Bocharov, A. V., Vishnyakova, T. G., Freeman, L. A., Kurlander, R. J., Patterson, A. P., Becker, L. C., & Remaley, A. T. (2013). Scavenger receptor-BI is a receptor for lipoprotein(a). Journal of Lipid Research, 54(9), 2450-2457. https://doi.org/10.1194/jlr.M038877