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 Resu...
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| Format: | Article |
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Wiley
2021-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.019820 |
| _version_ | 1811332674337374208 |
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| author | Kan Huang Chenshu Liu Meixiu Peng Qiao Su Ruiming Liu Zeling Guo Sifan Chen Zilun Li Guangqi Chang |
| author_facet | Kan Huang Chenshu Liu Meixiu Peng Qiao Su Ruiming Liu Zeling Guo Sifan Chen Zilun Li Guangqi Chang |
| author_sort | Kan Huang |
| collection | DOAJ |
| 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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| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T16:40:32Z |
| publishDate | 2021-04-01 |
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| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-f85a71417e164a788afa5c26a1aa104b2022-12-22T02:39:15ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-04-0110710.1161/JAHA.120.019820Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient MiceKan Huang0Chenshu Liu1Meixiu Peng2Qiao Su3Ruiming Liu4Zeling Guo5Sifan Chen6Zilun Li7Guangqi Chang8Division of Vascular Surgery First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaDivision of Vascular Surgery First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaDivision of Vascular Surgery First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaAnimal Center First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaNational‐Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaZhongshan School of Medicine Sun Yat‐sen University Guangzhou ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center Sun Yat‐Sen Memorial Hospital Guangzhou ChinaDivision of Vascular Surgery First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaDivision of Vascular Surgery First Affiliated Hospital, Sun Yat‐sen University Guangzhou ChinaBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.120.019820atherosclerosischolesterol homeostasisfoam cellglycoursodeoxycholic acidgut microbiota |
| spellingShingle | Kan Huang Chenshu Liu Meixiu Peng Qiao Su Ruiming Liu Zeling Guo Sifan Chen Zilun Li Guangqi Chang Glycoursodeoxycholic Acid Ameliorates Atherosclerosis and Alters Gut Microbiota in Apolipoprotein E–Deficient Mice Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atherosclerosis cholesterol homeostasis foam cell glycoursodeoxycholic acid gut microbiota |
| 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 | atherosclerosis cholesterol homeostasis foam cell glycoursodeoxycholic acid gut microbiota |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.019820 |
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