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Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1

ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid-poor apoproteins, has been implicated in macrophage lipid efflux and clearance of apoptotic cells in in vitro studies. In the current study, we investigated the in vivo effects of macrophage ABCA7 deficiency on lipid meta...

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Autores principales: Meurs, Illiana, Calpe-Berdiel, Laura, Habets, Kim L. L., Zhao, Ying, Korporaal, Suzanne J. A., Mommaas, A. Mieke, Josselin, Emmanuelle, Hildebrand, Reeni B., Ye, Dan, Out, Ruud, Kuiper, Johan, Van Berkel, Theo J. C., Chimini, Giovanna, Van Eck, Miranda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293875/
https://www.ncbi.nlm.nih.gov/pubmed/22403608
http://dx.doi.org/10.1371/journal.pone.0030984
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author Meurs, Illiana
Calpe-Berdiel, Laura
Habets, Kim L. L.
Zhao, Ying
Korporaal, Suzanne J. A.
Mommaas, A. Mieke
Josselin, Emmanuelle
Hildebrand, Reeni B.
Ye, Dan
Out, Ruud
Kuiper, Johan
Van Berkel, Theo J. C.
Chimini, Giovanna
Van Eck, Miranda
author_facet Meurs, Illiana
Calpe-Berdiel, Laura
Habets, Kim L. L.
Zhao, Ying
Korporaal, Suzanne J. A.
Mommaas, A. Mieke
Josselin, Emmanuelle
Hildebrand, Reeni B.
Ye, Dan
Out, Ruud
Kuiper, Johan
Van Berkel, Theo J. C.
Chimini, Giovanna
Van Eck, Miranda
author_sort Meurs, Illiana
collection PubMed
description ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid-poor apoproteins, has been implicated in macrophage lipid efflux and clearance of apoptotic cells in in vitro studies. In the current study, we investigated the in vivo effects of macrophage ABCA7 deficiency on lipid metabolism and atherosclerosis. Chimeras with dysfunctional ABCA7 in macrophages and other blood cells were generated by transplantation of bone marrow from ABCA7 knockout (KO) mice into irradiated low-density lipoprotein receptor (LDLr) KO mice. Unexpectedly, macrophage ABCA7 deficiency did not significantly affect atherosclerosis susceptibility of LDLr KO mice after 10 weeks Western-type diet feeding. However, ABCA7 deficiency was associated with 2-fold (p<0.05) higher macrophage ABCA1 mRNA expression levels. Combined disruption of ABCA1 and ABCA7 in bone-marrow-derived cells increased atherosclerotic lesion development (1.5-fold (p>0.05) as compared to wild type transplanted mice. However, single deletion of ABCA1 had a similar effect (1.8-fold, p<0.05). Macrophage foam cell accumulation in the peritoneal cavity was reduced in ABCA1/ABCA7 dKO transplanted animals as compared to single ABCA1 KO transplanted mice, which was associated with increased ABCG1 expression. Interestingly, spleens of ABCA1/ABCA7 double KO transplanted mice were significantly larger as compared to the other 3 groups and showed massive macrophage lipid accumulation, a reduction in CD3+ T-cells, and increased expression of key regulators of erythropoiesis. In conclusion, deletion of ABCA7 in bone marrow-derived cells does not affect atherogenesis in the arterial wall neither in the absence or presence of ABCA1. Interestingly, combined deletion of bone marrow ABCA1 and ABCA7 causes severe splenomegaly associated with cellular lipid accumulation, a reduction in splenic CD3+ T cells, and induced markers of erythropoeisis. Our data indicate that ABCA7 may play a role in T cell proliferation and erythropoeisis in spleen.
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spelling pubmed-32938752012-03-08 Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1 Meurs, Illiana Calpe-Berdiel, Laura Habets, Kim L. L. Zhao, Ying Korporaal, Suzanne J. A. Mommaas, A. Mieke Josselin, Emmanuelle Hildebrand, Reeni B. Ye, Dan Out, Ruud Kuiper, Johan Van Berkel, Theo J. C. Chimini, Giovanna Van Eck, Miranda PLoS One Research Article ABCA7, a close relative of ABCA1 which facilitates cholesterol efflux to lipid-poor apoproteins, has been implicated in macrophage lipid efflux and clearance of apoptotic cells in in vitro studies. In the current study, we investigated the in vivo effects of macrophage ABCA7 deficiency on lipid metabolism and atherosclerosis. Chimeras with dysfunctional ABCA7 in macrophages and other blood cells were generated by transplantation of bone marrow from ABCA7 knockout (KO) mice into irradiated low-density lipoprotein receptor (LDLr) KO mice. Unexpectedly, macrophage ABCA7 deficiency did not significantly affect atherosclerosis susceptibility of LDLr KO mice after 10 weeks Western-type diet feeding. However, ABCA7 deficiency was associated with 2-fold (p<0.05) higher macrophage ABCA1 mRNA expression levels. Combined disruption of ABCA1 and ABCA7 in bone-marrow-derived cells increased atherosclerotic lesion development (1.5-fold (p>0.05) as compared to wild type transplanted mice. However, single deletion of ABCA1 had a similar effect (1.8-fold, p<0.05). Macrophage foam cell accumulation in the peritoneal cavity was reduced in ABCA1/ABCA7 dKO transplanted animals as compared to single ABCA1 KO transplanted mice, which was associated with increased ABCG1 expression. Interestingly, spleens of ABCA1/ABCA7 double KO transplanted mice were significantly larger as compared to the other 3 groups and showed massive macrophage lipid accumulation, a reduction in CD3+ T-cells, and increased expression of key regulators of erythropoiesis. In conclusion, deletion of ABCA7 in bone marrow-derived cells does not affect atherogenesis in the arterial wall neither in the absence or presence of ABCA1. Interestingly, combined deletion of bone marrow ABCA1 and ABCA7 causes severe splenomegaly associated with cellular lipid accumulation, a reduction in splenic CD3+ T cells, and induced markers of erythropoeisis. Our data indicate that ABCA7 may play a role in T cell proliferation and erythropoeisis in spleen. Public Library of Science 2012-03-05 /pmc/articles/PMC3293875/ /pubmed/22403608 http://dx.doi.org/10.1371/journal.pone.0030984 Text en Meurs et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Meurs, Illiana
Calpe-Berdiel, Laura
Habets, Kim L. L.
Zhao, Ying
Korporaal, Suzanne J. A.
Mommaas, A. Mieke
Josselin, Emmanuelle
Hildebrand, Reeni B.
Ye, Dan
Out, Ruud
Kuiper, Johan
Van Berkel, Theo J. C.
Chimini, Giovanna
Van Eck, Miranda
Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title_full Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title_fullStr Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title_full_unstemmed Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title_short Effects of Deletion of Macrophage ABCA7 on Lipid Metabolism and the Development of Atherosclerosis in the Presence and Absence of ABCA1
title_sort effects of deletion of macrophage abca7 on lipid metabolism and the development of atherosclerosis in the presence and absence of abca1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293875/
https://www.ncbi.nlm.nih.gov/pubmed/22403608
http://dx.doi.org/10.1371/journal.pone.0030984
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