Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome
TMAO is a new risk biomarker for cardiovascular disease. With trimethylammonium as its main chemical skeleton, TMAO is structurally similar to many endogenous metabolites, such as acetylcholine, carnitine, phosphorylcholine, etc. The mechanism of TMAO on the pathological process of CVD is still uncl...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/9/3817 |
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| author | Dongyu Lei Wenbo Yu Yi Liu Yujie Jiang Xiaohui Li Jing Lv Ying Li |
| author_facet | Dongyu Lei Wenbo Yu Yi Liu Yujie Jiang Xiaohui Li Jing Lv Ying Li |
| author_sort | Dongyu Lei |
| collection | DOAJ |
| description | TMAO is a new risk biomarker for cardiovascular disease. With trimethylammonium as its main chemical skeleton, TMAO is structurally similar to many endogenous metabolites, such as acetylcholine, carnitine, phosphorylcholine, etc. The mechanism of TMAO on the pathological process of CVD is still unclear. In this study, the quantitative analysis of plasma TMAO is conducted, and the contribution of Cathepsin B and NLRP3 inflammasome during the process of TMAO-induced endothelial injury was proposed and investigated at animal and cellular levels. Immunofluorescence assay was applied to represent the protein expression of Cathepsin B and NLRP3 inflammasome located at endothelial cells. The results showed that TMAO could disrupt endothelial cells permeability to induce endothelial injury, meanwhile, TMAO could increase NLRP3 inflammasome activation and promote the activity and expression of Cathepsin B in vitro and in vivo, whereas inhibition of NLRP3 inflammasome activation by MCC950 could protect the endothelial cells from TMAO associated endothelial injury via Cathepsin B. The study reveals that TMAO can cause endothelial injury via Cathepsin B-dependent NLRP3 inflammasome, and inhibition of Cathepsin B and NLRP3 inflammasome can reduce the TMAO-induced damage. The results provide new insight into the role of TMAO in CVD, which can be a potential therapeutic target for disease treatment and drug design. |
| first_indexed | 2024-03-11T04:12:13Z |
| format | Article |
| id | doaj.art-72e5961a14b94d00bb602f4e152d92fd |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:12:13Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-72e5961a14b94d00bb602f4e152d92fd2023-11-17T23:23:51ZengMDPI AGMolecules1420-30492023-04-01289381710.3390/molecules28093817Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 InflammasomeDongyu Lei0Wenbo Yu1Yi Liu2Yujie Jiang3Xiaohui Li4Jing Lv5Ying Li6Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, ChinaDepartment of Health Management, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaTMAO is a new risk biomarker for cardiovascular disease. With trimethylammonium as its main chemical skeleton, TMAO is structurally similar to many endogenous metabolites, such as acetylcholine, carnitine, phosphorylcholine, etc. The mechanism of TMAO on the pathological process of CVD is still unclear. In this study, the quantitative analysis of plasma TMAO is conducted, and the contribution of Cathepsin B and NLRP3 inflammasome during the process of TMAO-induced endothelial injury was proposed and investigated at animal and cellular levels. Immunofluorescence assay was applied to represent the protein expression of Cathepsin B and NLRP3 inflammasome located at endothelial cells. The results showed that TMAO could disrupt endothelial cells permeability to induce endothelial injury, meanwhile, TMAO could increase NLRP3 inflammasome activation and promote the activity and expression of Cathepsin B in vitro and in vivo, whereas inhibition of NLRP3 inflammasome activation by MCC950 could protect the endothelial cells from TMAO associated endothelial injury via Cathepsin B. The study reveals that TMAO can cause endothelial injury via Cathepsin B-dependent NLRP3 inflammasome, and inhibition of Cathepsin B and NLRP3 inflammasome can reduce the TMAO-induced damage. The results provide new insight into the role of TMAO in CVD, which can be a potential therapeutic target for disease treatment and drug design.https://www.mdpi.com/1420-3049/28/9/3817Trimethylamine-N-OxideUPLC-MS/MSendothelialinjuryNLRP3 inflammasomeCathepsin B |
| spellingShingle | Dongyu Lei Wenbo Yu Yi Liu Yujie Jiang Xiaohui Li Jing Lv Ying Li Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome Molecules Trimethylamine-N-Oxide UPLC-MS/MS endothelialinjury NLRP3 inflammasome Cathepsin B |
| title | Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome |
| title_full | Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome |
| title_fullStr | Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome |
| title_full_unstemmed | Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome |
| title_short | Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome |
| title_sort | trimethylamine n oxide tmao inducing endothelial injury uplc ms ms based quantification and the activation of cathepsin b mediated nlrp3 inflammasome |
| topic | Trimethylamine-N-Oxide UPLC-MS/MS endothelialinjury NLRP3 inflammasome Cathepsin B |
| url | https://www.mdpi.com/1420-3049/28/9/3817 |
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