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Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta

Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-ti...

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Autores principales: Shchelkunova, Tatyana A., Morozov, Ivan A., Rubtsov, Petr M., Bobryshev, Yuri V., Sobenin, Igor A., Orekhov, Alexander N., Andrianova, Irina V., Smirnov, Alexander N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662660/
https://www.ncbi.nlm.nih.gov/pubmed/23717417
http://dx.doi.org/10.1371/journal.pone.0063374
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author Shchelkunova, Tatyana A.
Morozov, Ivan A.
Rubtsov, Petr M.
Bobryshev, Yuri V.
Sobenin, Igor A.
Orekhov, Alexander N.
Andrianova, Irina V.
Smirnov, Alexander N.
author_facet Shchelkunova, Tatyana A.
Morozov, Ivan A.
Rubtsov, Petr M.
Bobryshev, Yuri V.
Sobenin, Igor A.
Orekhov, Alexander N.
Andrianova, Irina V.
Smirnov, Alexander N.
author_sort Shchelkunova, Tatyana A.
collection PubMed
description Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRβ, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression.
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spelling pubmed-36626602013-05-28 Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta Shchelkunova, Tatyana A. Morozov, Ivan A. Rubtsov, Petr M. Bobryshev, Yuri V. Sobenin, Igor A. Orekhov, Alexander N. Andrianova, Irina V. Smirnov, Alexander N. PLoS One Research Article Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRβ, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression. Public Library of Science 2013-05-23 /pmc/articles/PMC3662660/ /pubmed/23717417 http://dx.doi.org/10.1371/journal.pone.0063374 Text en © 2013 Shchelkunova 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
Shchelkunova, Tatyana A.
Morozov, Ivan A.
Rubtsov, Petr M.
Bobryshev, Yuri V.
Sobenin, Igor A.
Orekhov, Alexander N.
Andrianova, Irina V.
Smirnov, Alexander N.
Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title_full Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title_fullStr Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title_full_unstemmed Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title_short Lipid Regulators during Atherogenesis: Expression of LXR, PPAR, and SREBP mRNA in the Human Aorta
title_sort lipid regulators during atherogenesis: expression of lxr, ppar, and srebp mrna in the human aorta
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662660/
https://www.ncbi.nlm.nih.gov/pubmed/23717417
http://dx.doi.org/10.1371/journal.pone.0063374
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