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PMID: 20488992 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 328 ·No. 5986 ·2010-06-25 ·Pages 1689-93

Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, Welch CL, Wang N, Randolph GJ, Snoeck HW, Tall AR

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.

MeSH Terms
ATP Binding Cassette Transporter 1 ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters/genetics,metabolism Animals Apolipoprotein A-I/genetics,metabolism Atherosclerosis/metabolism,physiopathology,therapy Bone Marrow Transplantation Cell Proliferation Cells, Cultured Cholesterol/metabolism Hematopoietic Stem Cells/physiology Hypercholesterolemia/metabolism Leukocytosis/metabolism,physiopathology,therapy Lipoproteins/genetics,metabolism Lipoproteins, HDL/metabolism Macrophages/metabolism Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Multipotent Stem Cells/physiology Myeloid Progenitor Cells/physiology Myeloproliferative Disorders/metabolism,physiopathology,therapy Phenotype Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism Receptors, Interleukin-3/metabolism Signal Transduction
Chemicals
ABCG1 protein, mouse ATP Binding Cassette Transporter 1 ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters Apolipoprotein A-I Lipoproteins Lipoproteins, HDL Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Receptors, Interleukin-3 Cholesterol
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Yvan-Charvet Laurent
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. [email protected]
Pagler Tamara
Gautier Emmanuel L
Avagyan Serine
Siry Read L
Han Seongah
Welch Carrie L
Wang Nan
Randolph Gwendalyn J
Snoeck Hans W
Tall Alan R
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1189731
Email
[email protected]
Published
2010-06-25
Epub
2010-00-20
Pages
1689-93
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3032591
Subset
IM
Grants
NHLBI NIH HHS · R01 HL073760 · United States
NIA NIH HHS · R01 AG016327 · United States
NIA NIH HHS · R01AG016327 · United States
NIAID NIH HHS · R01 AI061741 · United States
NIAID NIH HHS · R01 AI049653-10 · United States
PHS HHS · R01A1061741 · United States
NHLBI NIH HHS · HL54591 · United States
NIAID NIH HHS · R01 AI049653-09 · United States
NIA NIH HHS · R01 AG029626 · United States
NHLBI NIH HHS · P01 HL054591 · United States
NIAID NIH HHS · R01 AI061741-03 · United States
NIAID NIH HHS · R01 AI049653 · United States
NIAID NIH HHS · R01 AI061741-04 · United States
Corrections
CommentIn
PMID: 20576876
External Links
PubMed source DOI: 10.1126/science.1189731 PMC Full Text View journal details
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