ArticleAnnals of translational medicine2021
Trimethylamine-N-oxide-stimulated hepatocyte-derived exosomes promote inflammation and endothelial dysfunction through nuclear factor-kappa B signaling.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease as a Systemic Driver of Heart Failure With Preserved Ejection Fraction: Mechanistic Insights and Emerging Therapeutic Perspectives.Reviews in cardiovascular medicine · 2026Review
- Article
- Effects of probiotics on blood lipids, glucose and pressure in patients with coronary heart disease: a systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2026Review
- Role of Gut Microbiota in Diabetic HFpEF: Mechanisms and Therapeutic Implications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Gut microbiota-cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation.Nutrition & metabolism · 2025Review
- Trimethylamine-N-oxide damages astrocytes and lymphatic endothelial cells in the cerebral lymphatic system.IBRO neuroscience reports · 2025Article
- Decoding TMAO in the Gut-Organ Axis: From Biomarkers and Cell Death Mechanisms to Therapeutic Horizons.Drug design, development and therapy · 2025Review
- The gut microbiota-inflammation-HFpEF axis: deciphering the role of gut microbiota dysregulation in the pathogenesis and management of HFpEF.Frontiers in cellular and infection microbiology · 2025Review
- Microbiome-Derived Trimethylamine N-Oxide (TMAO) as a Multifaceted Biomarker in Cardiovascular Disease: Challenges and Opportunities.International journal of molecular sciences · 2024Review
- Gastrointestinal germinal center B cell depletion and reduction in IgAScience immunology · 2024Article
- Cardiovascular Disease May Be Triggered by Gut Microbiota, Microbial Metabolites, Gut Wall Reactions, and Inflammation.International journal of molecular sciences · 2024Review
- Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases.Cardiovascular & hematological disorders drug targets · 2024Review
- Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.Journal of clinical and translational hepatology · 2023Review
- The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases.Frontiers in endocrinology · 2023Review
- The role of the gut microbiota in health and cardiovascular diseases.Molecular biomedicine · 2022Review
- TMAO-Activated Hepatocyte-Derived Exosomes Are Widely Distributed in Mice with Different Patterns and Promote Vascular Inflammation.Cardiology research and practice · 2022Article
- TMAO-Activated Hepatocyte-Derived Exosomes Impair AngiogenesisFrontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrimethylamine-N-oxide (TMAO) has been proven to be a new proatherogenic compound for promoting inflammation and endothelial dysfunction. Hepatocyte-derived exosomes (Exos), including those derived from hepatocytes, play a pivotal role in the regulation of inflammation and endothelial function. As TMAO is produced in the liver, hepatocytes may be the potential target of TMAO. However, it is not yet clear whether TMAO can directly stimulate hepatocytes to produce Exos to mediate the detrimental effects of TMAO on vascular endothelial cells (VECs).
methodsHepatocytes treated with TMAO and Exos (TMAO-Exos) were isolated from the supernatant, and added to human aortic endothelial cells (HAECs). The expressions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were detected by quantitative polymerase chain reaction (qPCR). Cell apoptosis was evaluated using Hoechst 33342 staining and flow cytometry assay, and cell migration was assessed by scratch and transwell assay. C57BL/6 mice were treated with Exos for 24 h and the thoracic aortas were isolated, then the
resultsTMAO was found to stimulate hepatocytes to release Exos that could be taken up by HAECs, thus inducing inflammation and cell apoptosis, impairing cell migration, and inhibiting endothelium-dependent vasodilation. Additionally, the miRNAs such as miR-302d-3p carried by the TMAO-Exos were quite different to those in the TMAO-free group. A further analysis showed that the potential target genes for these miRNAs, such as mitogen-activated protein kinase 8, caspase 9 and BCL2-like 11, appeared to be involved with inflammation and endothelial function. Finally, we found that NF-κB signaling could be activated by TMAO-Exos.
conclusionsThese novel findings provide evidence that TMAO can indirectly talk to VECs by promoting hepatocytes to produce Exos that carry important genetic information.
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