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LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2

High cholesterol and diabetes are major risk factors for atherosclerosis. Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR) through the induction of genes involved in cholesterol transport and efflux. In the context of diabetes, regression of atherosclerosis is impaired...

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Autores principales: Hussein, Maryem A., Shrestha, Elina, Ouimet, Mireille, Barrett, Tessa J., Leone, Sarah, Moore, Kathryn J., Hérault, Yann, Fisher, Edward A., Garabedian, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545936/
https://www.ncbi.nlm.nih.gov/pubmed/26288135
http://dx.doi.org/10.1371/journal.pone.0135218
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author Hussein, Maryem A.
Shrestha, Elina
Ouimet, Mireille
Barrett, Tessa J.
Leone, Sarah
Moore, Kathryn J.
Hérault, Yann
Fisher, Edward A.
Garabedian, Michael J.
author_facet Hussein, Maryem A.
Shrestha, Elina
Ouimet, Mireille
Barrett, Tessa J.
Leone, Sarah
Moore, Kathryn J.
Hérault, Yann
Fisher, Edward A.
Garabedian, Michael J.
author_sort Hussein, Maryem A.
collection PubMed
description High cholesterol and diabetes are major risk factors for atherosclerosis. Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR) through the induction of genes involved in cholesterol transport and efflux. In the context of diabetes, regression of atherosclerosis is impaired. We proposed that changes in glucose levels modulate LXR-dependent gene expression. Using a mouse macrophage cell line (RAW 264.7) and primary bone marrow derived macrophages (BMDMs) cultured in normal or diabetes relevant high glucose conditions we found that high glucose inhibits the LXR-dependent expression of ATP-binding cassette transporter A1 (ABCA1), but not ABCG1. To probe for this mechanism, we surveyed the expression of a host of chromatin-modifying enzymes and found that Protein Arginine Methyltransferase 2 (PRMT2) was reduced in high compared to normal glucose conditions. Importantly, ABCA1 expression and ABCA1-mediated cholesterol efflux were reduced in Prmt2 (-/-) compared to wild type BMDMs. Monocytes from diabetic mice also showed decreased expression of Prmt2 compared to non-diabetic counterparts. Thus, PRMT2 represents a glucose-sensitive factor that plays a role in LXR-mediated ABCA1-dependent cholesterol efflux and lends insight to the presence of increased atherosclerosis in diabetic patients.
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spelling pubmed-45459362015-09-01 LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2 Hussein, Maryem A. Shrestha, Elina Ouimet, Mireille Barrett, Tessa J. Leone, Sarah Moore, Kathryn J. Hérault, Yann Fisher, Edward A. Garabedian, Michael J. PLoS One Research Article High cholesterol and diabetes are major risk factors for atherosclerosis. Regression of atherosclerosis is mediated in part by the Liver X Receptor (LXR) through the induction of genes involved in cholesterol transport and efflux. In the context of diabetes, regression of atherosclerosis is impaired. We proposed that changes in glucose levels modulate LXR-dependent gene expression. Using a mouse macrophage cell line (RAW 264.7) and primary bone marrow derived macrophages (BMDMs) cultured in normal or diabetes relevant high glucose conditions we found that high glucose inhibits the LXR-dependent expression of ATP-binding cassette transporter A1 (ABCA1), but not ABCG1. To probe for this mechanism, we surveyed the expression of a host of chromatin-modifying enzymes and found that Protein Arginine Methyltransferase 2 (PRMT2) was reduced in high compared to normal glucose conditions. Importantly, ABCA1 expression and ABCA1-mediated cholesterol efflux were reduced in Prmt2 (-/-) compared to wild type BMDMs. Monocytes from diabetic mice also showed decreased expression of Prmt2 compared to non-diabetic counterparts. Thus, PRMT2 represents a glucose-sensitive factor that plays a role in LXR-mediated ABCA1-dependent cholesterol efflux and lends insight to the presence of increased atherosclerosis in diabetic patients. Public Library of Science 2015-08-19 /pmc/articles/PMC4545936/ /pubmed/26288135 http://dx.doi.org/10.1371/journal.pone.0135218 Text en © 2015 Hussein 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
Hussein, Maryem A.
Shrestha, Elina
Ouimet, Mireille
Barrett, Tessa J.
Leone, Sarah
Moore, Kathryn J.
Hérault, Yann
Fisher, Edward A.
Garabedian, Michael J.
LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title_full LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title_fullStr LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title_full_unstemmed LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title_short LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
title_sort lxr-mediated abca1 expression and function are modulated by high glucose and prmt2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545936/
https://www.ncbi.nlm.nih.gov/pubmed/26288135
http://dx.doi.org/10.1371/journal.pone.0135218
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