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Science. 2010 Jun 25;328(5986):1689-93. doi: 10.1126/science.1189731. Epub 2010 May 20.

ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.

Author information

1
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. ly2159@columbia.edu

Abstract

Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate-binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin(-)Sca-1(+)Kit+ (LSK) in the bone marrow. Transplantation of Abca1(-/-) Abcg1(-/-) bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.

PMID:
20488992
PMCID:
PMC3032591
DOI:
10.1126/science.1189731
[Indexed for MEDLINE]
Free PMC Article

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