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Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice

Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates... Basic Sciences Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice Andrew J. Murphy,* Vincent Sarrazy,* Nan Wang, Nora Bijl, Sandra Abramowicz, Marit Westerterp, Carrie B. Welch, John D. Schuetz, Laurent Yvan-Charvet 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. Approach and 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice

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Copyright
© 2014 American Heart Association, Inc.
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.113.302613
pmid
24504733
Publisher site
See Article on Publisher Site

Abstract

Basic Sciences Deficiency of ATP-Binding Cassette Transporter B6 in Megakaryocyte Progenitors Accelerates Atherosclerosis in Mice Andrew J. Murphy,* Vincent Sarrazy,* Nan Wang, Nora Bijl, Sandra Abramowicz, Marit Westerterp, Carrie B. Welch, John D. Schuetz, Laurent Yvan-Charvet 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. Approach and 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

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health

Published: Apr 1, 2014

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