ArticleFrontiers in pharmacology2021
Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Multi-Omics Mechanisms of Trimethylamine Oxide and Cardiovascular Disease: A Review.Reviews in cardiovascular medicine · 2026Review
- TMAO and the gut microbiome: implications for the CVD-CKD-IBD axis.Annals of medicine · 2025Review
- From Gut to Heart: Targeting Trimethylamine N-Oxide as a Novel Strategy in Heart Failure Management.Biomolecules · 2025Review
- Sex-specific cardiac dysfunction in mice with chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies.Acta pharmacologica Sinica · 2025Review
- 3,3-Dimethyl-1-Butanol and its Metabolite 3,3-Dimethylbutyrate Ameliorate Collagen-induced Arthritis Independent of Choline Trimethylamine Lyase Activity.Inflammation · 2025Article
- Acute kidney injury after myocardial infarction: prognostic implications via dual robust methods.Frontiers in medicine · 2025Article
- Unlocking Cardioprotective Potential of Gut Microbiome: Exploring Therapeutic Strategies.Journal of microbiology and biotechnology · 2024Review
- Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.Cardiovascular toxicology · 2024Article
- Trimethylamine N-oxide: a meta-organismal axis linking the gut and fibrosis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Role of Trimethylamine N-Oxide in Heart Failure.Reviews in cardiovascular medicine · 2024Review
- Gut Microbiome and Its Role in Valvular Heart Disease: Not a "Gutted" Relationship.Life (Basel, Switzerland) · 2024Review
- Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms.Gut microbes · 2023Review
- Probiotics as potential treatments to reduce myocardial remodelling and heart failure via the gut-heart axis: State-of-the-art review.Molecular and cellular biochemistry · 2023Review
- Article
- The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction.Journal of cardiovascular development and disease · 2023Article
- Review
- From heart failure and kidney dysfunction to cardiorenal syndrome: TMAO may be a bridge.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic heart failure (HF) frequently causes progressive decline in kidney function, known as cardiorenal syndrome-2 (CRS2). Current treatment options for CRS2 remain unacceptably limited. Trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota, has recently been implicated in the pathogenesis of both HF and chronic kidney disease. Here we examined whether circulating TMAO is elevated in CRS2 and if so, whether attenuation of circulating TMAO would ameliorate the progression of CRS2. Sprague-Dawley rats underwent surgery for myocardial infarction (MI) or sham (week 0) followed by subtotal (5/6) nephrectomy (STNx) or sham at week 4 to induce CRS2 or control. At week 6, MI + STNx rats and control rats received vehicle or 1.0% 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) treatment for 8 weeks. Compared with control rats, MI + STNx rats exhibited elevated serum TMAO at week 6, which was increased further at week 14 but was attenuated by DMB treatment. MI + STNx rats showed cardiac dysfunction as assessed by echocardiography and renal dysfunction as evidenced by increased serum creatinine and urinary kidney injury molecule-1 and decreased creatinine clearance at week 6. The cardiac and renal dysfunction in MI + STNx rats was exacerbated at week 14 but was prevented by DMB treatment. Molecular and histological studies revealed myocyte hypertrophy and increases in interstitial myocardial fibrosis and gene expression of pro-hypertrophic and pro-fibrotic markers in both heart and kidney at week 14, which were accompanied by elevated gene expression of proinflammatory cytokines. The changes in molecular and histological parameters observed in MI + STNx rats were significantly reduced by DMB treatment. These findings suggest that rats with CRS2 have elevated circulating TMAO, which is associated with the exacerbation of cardiac and renal dysfunction. Attenuation of circulating TMAO can ameliorate cardiac and renal injury and prevents the progression of CRS2.
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Registered trials
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