ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins

Proceedings of the National Academy of Sciences of the United States of America - Tập 101 Số 26 - Trang 9774-9779 - 2004
Nan Wang1, Debin Lan1, Wengen Chen1, Fumihiko Matsuura1, Alan R. Tall1
1Department of Medicine, Division of Molecular Medicine, Columbia University, New York, NY 10032

Tóm tắt

The mechanisms responsible for the inverse relationship between plasma high-density lipoprotein (HDL) levels and atherosclerotic cardiovascular disease are poorly understood. The ATP-binding cassette transporter A1 (ABCA1) mediates efflux of cellular cholesterol to lipid-poor apolipoproteins but not to HDL particles that constitute the bulk of plasma HDL. We show that two ABC transporters of unknown function, ABCG1 and ABCG4, mediate isotopic and net mass efflux of cellular cholesterol to HDL. In transfected 293 cells, ABCG1 and ABCG4 stimulate cholesterol efflux to both smaller (HDL-3) and larger (HDL-2) subclasses but not to lipid-poor apoA-I. Treatment of macrophages with an liver X receptor activator results in up-regulation of ABCG1 and increases cholesterol efflux to HDL. RNA interference reduced the expression of ABCG1 in liver X receptor-activated macrophages and caused a parallel decrease in cholesterol efflux to HDL. These studies indicate that ABCG1 and ABCG4 promote cholesterol efflux from cells to HDL. ABCG1 is highly expressed in macrophages and probably mediates cholesterol efflux from macrophage foam cells to the major HDL fractions, providing a mechanism to explain the relationship between HDL levels and atherosclerosis risk.

Từ khóa


Tài liệu tham khảo

10.1038/72869

10.1038/11921

10.1038/11914

10.1038/11905

10.1074/jbc.M005438200

10.1074/jbc.M006738200

10.1074/jbc.M102348200

10.1172/JCI117603

10.1074/jbc.M003337200

10.1126/science.289.5484.1524

10.1074/jbc.M107938200

10.1126/science.290.5497.1771

10.1074/jbc.M109927200

10.1074/jbc.M301311200

10.1074/jbc.M105863200

10.1093/eurheartj/11.suppl_E.230

10.1021/bi035813p

10.1194/jlr.M300355-JLR200

10.1172/JCI14011

10.1006/bbrc.2001.5756

10.1073/pnas.97.2.817

10.1038/nbt831

10.1016/S0022-2275(20)32205-7

Brewer, H. B., Jr., & Santamarina-Fojo, S. (2003) Am. J. Cardiol. 91, 3E-11E.

10.1358/dnp.2003.16.8.829346

10.1074/jbc.M301189200

10.1016/S0167-4889(02)00269-0

10.1016/0005-2760(94)00232-N

10.1016/S0022-2275(20)31605-9

10.1074/jbc.M300760200

10.1074/jbc.272.34.20982

10.1161/01.CIR.0000093189.97429.9D

10.1074/jbc.M310223200

10.1074/jbc.M310785200

10.1007/s003359900203

10.1016/S0378-1119(96)00633-6

10.1016/S0021-9258(18)89830-1

10.1161/01.ATV.0000057572.97137.DD

10.1074/jbc.271.27.16026

10.1074/jbc.M108861200

10.1056/NEJM199108083250601

10.1093/hmg/ddh119

10.1001/jama.290.17.2292

10.1172/JCI108833

10.1172/JCI114132

10.1056/NEJMoa031766

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 101 Số 26

9774-9779

Thông tin tác giả