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Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice

BACKGROUND: Although glycoursodeoxycholic acid (GUDCA) has been associated with the improvement of metabolic disorders, its effect on atherosclerosis remains elusive. This study aimed to investigate the role of GUDCA in the development of atherosclerosis and its potential mechanisms. METHODS AND RES...

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Autores principales: Huang, Kan, Liu, Chenshu, Peng, Meixiu, Su, Qiao, Liu, Ruiming, Guo, Zeling, Chen, Sifan, Li, Zilun, Chang, Guangqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174342/
https://www.ncbi.nlm.nih.gov/pubmed/33787322
http://dx.doi.org/10.1161/JAHA.120.019820
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author Huang, Kan
Liu, Chenshu
Peng, Meixiu
Su, Qiao
Liu, Ruiming
Guo, Zeling
Chen, Sifan
Li, Zilun
Chang, Guangqi
author_facet Huang, Kan
Liu, Chenshu
Peng, Meixiu
Su, Qiao
Liu, Ruiming
Guo, Zeling
Chen, Sifan
Li, Zilun
Chang, Guangqi
author_sort Huang, Kan
collection PubMed
description BACKGROUND: Although glycoursodeoxycholic acid (GUDCA) has been associated with the improvement of metabolic disorders, its effect on atherosclerosis remains elusive. This study aimed to investigate the role of GUDCA in the development of atherosclerosis and its potential mechanisms. METHODS AND RESULTS: Human THP‐1 macrophages were used to investigate the effect of GUDCA on oxidized low‐density lipoprotein–induced foam cell formation in vitro. We found that GUDCA downregulated scavenger receptor A1 mRNA expression, reduced oxidized low‐density lipoprotein uptake, and inhibited macrophage foam cell formation. In an in vivo study, apolipoprotein E–deficient mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then were gavaged once daily with or without GUDCA for 18 weeks. Parameters of systemic metabolism and atherosclerosis were detected. We found that GUDCA improved cholesterol homeostasis and protected against atherosclerosis progression as evidenced by reduced plaque area along with lipid deposition, ameliorated local chronic inflammation, and elevated plaque stability. In addition, 16S rDNA sequencing showed that GUDCA administration partially normalized the Western diet–associated gut microbiota dysbiosis. Interestingly, the changes of bacterial genera (Alloprevotella, Parabacteroides, Turicibacter, and Alistipes) modulated by GUDCA were correlated with the plaque area in mice aortas. CONCLUSIONS: Our study for the first time indicates that GUDCA attenuates the development of atherosclerosis, probably attributable to the inhibition of foam cell formation, maintenance of cholesterol homeostasis, and modulation of gut microbiota.
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spelling pubmed-81743422021-06-11 Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice Huang, Kan Liu, Chenshu Peng, Meixiu Su, Qiao Liu, Ruiming Guo, Zeling Chen, Sifan Li, Zilun Chang, Guangqi J Am Heart Assoc Original Research BACKGROUND: Although glycoursodeoxycholic acid (GUDCA) has been associated with the improvement of metabolic disorders, its effect on atherosclerosis remains elusive. This study aimed to investigate the role of GUDCA in the development of atherosclerosis and its potential mechanisms. METHODS AND RESULTS: Human THP‐1 macrophages were used to investigate the effect of GUDCA on oxidized low‐density lipoprotein–induced foam cell formation in vitro. We found that GUDCA downregulated scavenger receptor A1 mRNA expression, reduced oxidized low‐density lipoprotein uptake, and inhibited macrophage foam cell formation. In an in vivo study, apolipoprotein E–deficient mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then were gavaged once daily with or without GUDCA for 18 weeks. Parameters of systemic metabolism and atherosclerosis were detected. We found that GUDCA improved cholesterol homeostasis and protected against atherosclerosis progression as evidenced by reduced plaque area along with lipid deposition, ameliorated local chronic inflammation, and elevated plaque stability. In addition, 16S rDNA sequencing showed that GUDCA administration partially normalized the Western diet–associated gut microbiota dysbiosis. Interestingly, the changes of bacterial genera (Alloprevotella, Parabacteroides, Turicibacter, and Alistipes) modulated by GUDCA were correlated with the plaque area in mice aortas. CONCLUSIONS: Our study for the first time indicates that GUDCA attenuates the development of atherosclerosis, probably attributable to the inhibition of foam cell formation, maintenance of cholesterol homeostasis, and modulation of gut microbiota. John Wiley and Sons Inc. 2021-03-31 /pmc/articles/PMC8174342/ /pubmed/33787322 http://dx.doi.org/10.1161/JAHA.120.019820 Text en © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Huang, Kan
Liu, Chenshu
Peng, Meixiu
Su, Qiao
Liu, Ruiming
Guo, Zeling
Chen, Sifan
Li, Zilun
Chang, Guangqi
Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title_full Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title_fullStr Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title_full_unstemmed Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title_short Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice
title_sort glycoursodeoxycholic acid ameliorates atherosclerosis and alters gut microbiota in apolipoprotein e–deficient mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174342/
https://www.ncbi.nlm.nih.gov/pubmed/33787322
http://dx.doi.org/10.1161/JAHA.120.019820
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