DCA-TGR5 signaling activation alleviates inflammatory response and improves cardiac function in myocardial infarction
Copyright © 2020. Published by Elsevier Ltd..
AIMS: The progression of myocardial infarction (MI) involves multiple metabolic disorders. Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate multiple cardiovascular functions. G protein-coupled bile acid receptor (TGR5) is one of the receptors sensing bile acids to mediate their biological functions. In this study, we aimed to elucidate the effects of bile acids-TGR5 signaling pathways in myocardial infarction (MI).
METHODS AND RESULTS: Blood samples of AMI patients or control subjects were collected and plasma was used for bile acid metabolism analysis. We discovered that bile acid levels were altered and deoxycholic acid (DCA) was substantially reduced in the plasma of AMI patients. Mice underwent either the LAD ligation model of MI or sham operation. Both MI and sham mice were gavaged with 10 mg/kg/d DCA or vehicle control since 3-day before the operation. Cardiac function was assessed by ultrasound echocardiography, infarct area was evaluated by TTC staining and Masson trichrome staining. Administration of DCA improved cardiac function and reduced ischemic injury at the 7th-day post-MI. The effects of DCA were dependent on binding to its receptor TGR5. Tgr5-/- mice underwent the same MI model. Cardiac function deteriorated and infarct size was increased at the 7th-day post-MI, which were not savaged by DCA administration. Moreover, DCA inhibited interleukin (IL)-1β expression in the infarcted hearts, and ameliorated IL-1β activation at 1-day post-MI. DCA inhibited NF-κB signaling and further IL-1β expression in cultured neonatal mouse cardiomyocytes under hypoxia as well as cardio-fibroblasts with the treatment of LPS.
CONCLUSIONS: DCA-TGR5 signaling pathway activation decreases inflammation and ameliorates heart function post-infarction. Strategies that control bile acid metabolism and TGR5 signaling to ameliorate the inflammatory responses may provide beneficial effects in patients with myocardial infarction.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:151 |
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Enthalten in: |
Journal of molecular and cellular cardiology - 151(2021) vom: 01. Feb., Seite 3-14 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wang, Jiaxing [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 06.10.2021 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.yjmcc.2020.10.014 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM316985988 |
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100 | 1 | |a Wang, Jiaxing |e verfasserin |4 aut | |
245 | 1 | 0 | |a DCA-TGR5 signaling activation alleviates inflammatory response and improves cardiac function in myocardial infarction |
264 | 1 | |c 2021 | |
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500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2020. Published by Elsevier Ltd. | ||
520 | |a AIMS: The progression of myocardial infarction (MI) involves multiple metabolic disorders. Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate multiple cardiovascular functions. G protein-coupled bile acid receptor (TGR5) is one of the receptors sensing bile acids to mediate their biological functions. In this study, we aimed to elucidate the effects of bile acids-TGR5 signaling pathways in myocardial infarction (MI) | ||
520 | |a METHODS AND RESULTS: Blood samples of AMI patients or control subjects were collected and plasma was used for bile acid metabolism analysis. We discovered that bile acid levels were altered and deoxycholic acid (DCA) was substantially reduced in the plasma of AMI patients. Mice underwent either the LAD ligation model of MI or sham operation. Both MI and sham mice were gavaged with 10 mg/kg/d DCA or vehicle control since 3-day before the operation. Cardiac function was assessed by ultrasound echocardiography, infarct area was evaluated by TTC staining and Masson trichrome staining. Administration of DCA improved cardiac function and reduced ischemic injury at the 7th-day post-MI. The effects of DCA were dependent on binding to its receptor TGR5. Tgr5-/- mice underwent the same MI model. Cardiac function deteriorated and infarct size was increased at the 7th-day post-MI, which were not savaged by DCA administration. Moreover, DCA inhibited interleukin (IL)-1β expression in the infarcted hearts, and ameliorated IL-1β activation at 1-day post-MI. DCA inhibited NF-κB signaling and further IL-1β expression in cultured neonatal mouse cardiomyocytes under hypoxia as well as cardio-fibroblasts with the treatment of LPS | ||
520 | |a CONCLUSIONS: DCA-TGR5 signaling pathway activation decreases inflammation and ameliorates heart function post-infarction. Strategies that control bile acid metabolism and TGR5 signaling to ameliorate the inflammatory responses may provide beneficial effects in patients with myocardial infarction | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a DCA | |
650 | 4 | |a Inflammation | |
650 | 4 | |a Myocardial infarction | |
650 | 4 | |a TGR5 | |
650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
650 | 7 | |a Gpbar1 protein, mouse |2 NLM | |
650 | 7 | |a Reactive Oxygen Species |2 NLM | |
650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
650 | 7 | |a Deoxycholic Acid |2 NLM | |
650 | 7 | |a 005990WHZZ |2 NLM | |
700 | 1 | |a Zhang, Jianshu |e verfasserin |4 aut | |
700 | 1 | |a Lin, Xianjuan |e verfasserin |4 aut | |
700 | 1 | |a Wang, Yupeng |e verfasserin |4 aut | |
700 | 1 | |a Wu, Xiang |e verfasserin |4 aut | |
700 | 1 | |a Yang, Fan |e verfasserin |4 aut | |
700 | 1 | |a Gao, Wei |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
700 | 1 | |a Sun, Jinpeng |e verfasserin |4 aut | |
700 | 1 | |a Jiang, Changtao |e verfasserin |4 aut | |
700 | 1 | |a Xu, Ming |e verfasserin |4 aut | |
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