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

Identifieur interne : 001778 ( Ncbi/Merge ); précédent : 001777; suivant : 001779

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

Descripteurs français

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

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pubmed:24504733

Le document en format XML

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<term>Atherosclerosis (genetics)</term>
<term>Atherosclerosis (metabolism)</term>
<term>Atherosclerosis (pathology)</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>
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<Volume>34</Volume>
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<Month>Apr</Month>
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<Title>Arteriosclerosis, thrombosis, and vascular biology</Title>
<ISOAbbreviation>Arterioscler. Thromb. Vasc. Biol.</ISOAbbreviation>
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<ArticleTitle>Deficiency of ATP-binding cassette transporter B6 in megakaryocyte progenitors accelerates atherosclerosis in mice.</ArticleTitle>
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<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>
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<DescriptorName UI="D017382" MajorTopicYN="N">Reactive Oxygen Species</DescriptorName>
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<name sortKey="Abramowicz, Sandra" sort="Abramowicz, Sandra" uniqKey="Abramowicz S" first="Sandra" last="Abramowicz">Sandra Abramowicz</name>
<name sortKey="Bijl, Nora" sort="Bijl, Nora" uniqKey="Bijl N" first="Nora" last="Bijl">Nora Bijl</name>
<name sortKey="Murphy, Andrew J" sort="Murphy, Andrew J" uniqKey="Murphy A" first="Andrew J" last="Murphy">Andrew J. Murphy</name>
<name sortKey="Sarrazy, Vincent" sort="Sarrazy, Vincent" uniqKey="Sarrazy V" first="Vincent" last="Sarrazy">Vincent Sarrazy</name>
<name sortKey="Schuetz, John D" sort="Schuetz, John D" uniqKey="Schuetz J" first="John D" last="Schuetz">John D. Schuetz</name>
<name sortKey="Wang, Nan" sort="Wang, Nan" uniqKey="Wang N" first="Nan" last="Wang">Nan Wang</name>
<name sortKey="Welch, Carrie B" sort="Welch, Carrie B" uniqKey="Welch C" first="Carrie B" last="Welch">Carrie B. Welch</name>
<name sortKey="Westerterp, Marit" sort="Westerterp, Marit" uniqKey="Westerterp M" first="Marit" last="Westerterp">Marit Westerterp</name>
<name sortKey="Yvan Charvet, Laurent" sort="Yvan Charvet, Laurent" uniqKey="Yvan Charvet L" first="Laurent" last="Yvan-Charvet">Laurent Yvan-Charvet</name>
</noCountry>
</tree>
</affiliations>
</record>

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