title: ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.
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.
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. ly2159@columbia.edu
authors.forename: Laurent
authors.initials: L
authors.lastname: Yvan-Charvet
authors.forename: Tamara
authors.initials: T
authors.lastname: Pagler
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Serine
authors.initials: S
authors.lastname: Avagyan
authors.forename: Read L
authors.initials: RL
authors.lastname: Siry
authors.forename: Seongah
authors.initials: S
authors.lastname: Han
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Welch
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Hans W
authors.initials: HW
authors.lastname: Snoeck
authors.forename: Alan R
authors.initials: AR
authors.lastname: Tall
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006937:Hypercholesterolemia / Q000378:metabolism; D007964:Leukocytosis / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000502:physiology; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D009196:Myeloproliferative Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010641:Phenotype; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D002784:Cholesterol