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Deficiency of ATP-binding cassette transporter B6 in megakaryocyte progenitors accelerates atherosclerosis in mice.

Identifieur interne : 003837 ( PubMed/Corpus ); précédent : 003836; suivant : 003838

Deficiency of ATP-binding cassette transporter B6 in megakaryocyte progenitors accelerates atherosclerosis in mice.

Auteurs : Andrew J. Murphy ; Vincent Sarrazy ; Nan Wang ; Nora Bijl ; Sandra Abramowicz ; Marit Westerterp ; Carrie B. Welch ; John D. Schuetz ; Laurent Yvan-Charvet

Source :

RBID : pubmed:24504733

English descriptors

Abstract

The ATP-binding cassette (ABC) transporter B6 (ABCB6) is highly expressed in megakaryocyte progenitors, but its role in platelet production and disease has not been elucidated.

DOI: 10.1161/ATVBAHA.113.302613
PubMed: 24504733

Links to Exploration step

pubmed:24504733

Le document en format XML

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<nlm:affiliation>From Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (A.J.M.); Department of Immunology, Monash University, Melbourne, Australia (A.J.M.); Institut National de la Sante et de la Recherche Medicale U1065, Centre Mediterraneen de Medecine Molecuaire (C3M), Atip-Avenir, Nice, France (V.S., L.Y.-C.); Department of Medicine, Division of Molecular Medicine, Columbia University, New York, NY (N.W., N.B., S.A., M.W., C.B.W.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN (J.D.S.).</nlm:affiliation>
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<name sortKey="Wang, Nan" sort="Wang, Nan" uniqKey="Wang N" first="Nan" last="Wang">Nan Wang</name>
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<name sortKey="Welch, Carrie B" sort="Welch, Carrie B" uniqKey="Welch C" first="Carrie B" last="Welch">Carrie B. Welch</name>
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<term>ATP-Binding Cassette Transporters (deficiency)</term>
<term>ATP-Binding Cassette Transporters (genetics)</term>
<term>Animals</term>
<term>Atherosclerosis (blood)</term>
<term>Atherosclerosis (genetics)</term>
<term>Atherosclerosis (metabolism)</term>
<term>Atherosclerosis (pathology)</term>
<term>Atherosclerosis (prevention & control)</term>
<term>Blood Platelets (metabolism)</term>
<term>Bone Marrow Transplantation</term>
<term>Cell Proliferation</term>
<term>Cells, Cultured</term>
<term>Chemokine CCL5 (metabolism)</term>
<term>Disease Models, Animal</term>
<term>Disease Progression</term>
<term>Female</term>
<term>Gene Expression Regulation</term>
<term>Megakaryocyte Progenitor Cells (metabolism)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Platelet Activation</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Receptors, LDL (genetics)</term>
<term>Receptors, LDL (metabolism)</term>
<term>Thrombopoiesis</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Receptors, LDL</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Chemokine CCL5</term>
<term>Reactive Oxygen Species</term>
<term>Receptors, LDL</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en">
<term>Atherosclerosis</term>
</keywords>
<keywords scheme="MESH" qualifier="deficiency" xml:lang="en">
<term>ATP-Binding Cassette Transporters</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>ATP-Binding Cassette Transporters</term>
<term>Atherosclerosis</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Atherosclerosis</term>
<term>Blood Platelets</term>
<term>Megakaryocyte Progenitor Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Atherosclerosis</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Atherosclerosis</term>
</keywords>
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<term>Bone Marrow Transplantation</term>
<term>Cell Proliferation</term>
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<term>Disease Progression</term>
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<term>Gene Expression Regulation</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Platelet Activation</term>
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<front>
<div type="abstract" xml:lang="en">The ATP-binding cassette (ABC) transporter B6 (ABCB6) is highly expressed in megakaryocyte progenitors, but its role in platelet production and disease has not been elucidated.</div>
</front>
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<DateCreated>
<Year>2014</Year>
<Month>03</Month>
<Day>25</Day>
</DateCreated>
<DateCompleted>
<Year>2014</Year>
<Month>05</Month>
<Day>19</Day>
</DateCompleted>
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<Year>2014</Year>
<Month>12</Month>
<Day>19</Day>
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<ISSN IssnType="Electronic">1524-4636</ISSN>
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<Volume>34</Volume>
<Issue>4</Issue>
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<Year>2014</Year>
<Month>Apr</Month>
</PubDate>
</JournalIssue>
<Title>Arteriosclerosis, thrombosis, and vascular biology</Title>
<ISOAbbreviation>Arterioscler. Thromb. Vasc. Biol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Deficiency of ATP-binding cassette transporter B6 in megakaryocyte progenitors accelerates atherosclerosis in mice.</ArticleTitle>
<Pagination>
<MedlinePgn>751-8</MedlinePgn>
</Pagination>
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<Abstract>
<AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The ATP-binding cassette (ABC) transporter B6 (ABCB6) is highly expressed in megakaryocyte progenitors, but its role in platelet production and disease has not been elucidated.</AbstractText>
<AbstractText Label="APPROACH AND RESULTS" NlmCategory="RESULTS">Among various ABC transporters, ABCB6 was highly expressed in megakaryocyte progenitors, exhibiting the same pattern of expression of genes involved in heme synthesis pathway. Transplantation of Abcb6 deficient (Abcb6(-/-)) bone marrow into low density lipoprotein receptor deficient recipient mice resulted in expansion and proliferation of megakaryocyte progenitors, attributable to increased reactive oxygen species production in response to porphyrin loading. The enhanced megakaryopoiesis in Abcb6(-/-) bone marrow-transplanted mice was further illustrated by increased platelet counts, mean platelet volume, and platelet activity. Platelets from Abcb6(-/-) bone marrow-transplanted mice had higher levels of chemokine (C-C motif) ligand 5, which was associated with increased plasma chemokine (C-C motif) ligand 5 levels. There were also increased platelet-leukocyte aggregates, which resulted in leukocyte activation. Abcb6(-/-) bone marrow-transplanted mice had accelerated atherosclerosis which was associated with deposition of the chemotactic agent, chemokine (C-C motif) ligand 5 in atherosclerotic plaques, resulting in increased macrophage accumulation.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our findings identify a new role of ABCB6 in preventing atherosclerosis development by dampening platelet production, reactivity, and chemokine (C-C motif) ligand 5 deposition in atherosclerotic lesions.</AbstractText>
</Abstract>
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<Affiliation>From Haematopoiesis and Leukocyte Biology, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (A.J.M.); Department of Immunology, Monash University, Melbourne, Australia (A.J.M.); Institut National de la Sante et de la Recherche Medicale U1065, Centre Mediterraneen de Medecine Molecuaire (C3M), Atip-Avenir, Nice, France (V.S., L.Y.-C.); Department of Medicine, Division of Molecular Medicine, Columbia University, New York, NY (N.W., N.B., S.A., M.W., C.B.W.); and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN (J.D.S.).</Affiliation>
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<Language>eng</Language>
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<Month>02</Month>
<Day>06</Day>
</ArticleDate>
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<Country>United States</Country>
<MedlineTA>Arterioscler Thromb Vasc Biol</MedlineTA>
<NlmUniqueID>9505803</NlmUniqueID>
<ISSNLinking>1079-5642</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C514489">Abcb6 protein, mouse</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C503460">Ccl5 protein, mouse</NameOfSubstance>
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<RefSource>Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):700-1</RefSource>
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<Keyword MajorTopicYN="N">ATP binding cassette transporter</Keyword>
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<Keyword MajorTopicYN="N">platelet</Keyword>
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