» Articles » PMID: 34387163

Pathogenic Mechanisms of Trimethylamine N-Oxide-induced Atherosclerosis and Cardiomyopathy

Overview
Date 2021 Aug 13
PMID 34387163
Citations 16
Authors
Affiliations
Soon will be listed here.
Abstract

Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.

Citing Articles

Short-Chain Fatty Acids and Their Metabolic Interactions in Heart Failure.

Chulenbayeva L, Issilbayeva A, Sailybayeva A, Bekbossynova M, Kozhakhmetov S, Kushugulova A Biomedicines. 2025; 13(2).

PMID: 40002756 PMC: 11853371. DOI: 10.3390/biomedicines13020343.


Urinary Metabolite Profiles of Participants with Overweight and Obesity Prescribed a Weight Loss High Fruit and Vegetable Diet: A Single Arm Intervention Study.

Clarke E, Gomez-Martin M, Stanford J, Yilmaz A, Ustun I, Wood L Nutrients. 2025; 16(24.

PMID: 39770979 PMC: 11677377. DOI: 10.3390/nu16244358.


A Narrative Review of the Role of Blood Biomarkers in the Risk Prediction of Cardiovascular Diseases.

Garady L, Soota A, Shouche Y, Chandrachari K, K V S, Shankar P Cureus. 2025; 16(12):e74899.

PMID: 39742176 PMC: 11688159. DOI: 10.7759/cureus.74899.


Intestinal Microbiota and Aging in People with HIV-What We Know and What We Don't.

Islam S, Singh S, Keshavarzian A, Abdel-Mohsen M Curr HIV/AIDS Rep. 2024; 22(1):9.

PMID: 39666149 PMC: 11874070. DOI: 10.1007/s11904-024-00717-w.


Inulin does not affect trimethylamine N-oxide formation in mice with a high-fat diet combined with choline and L-carnitine.

Wang X, Hu X, He W, Yin J Food Sci Nutr. 2024; 12(11):8968-8977.

PMID: 39619951 PMC: 11606906. DOI: 10.1002/fsn3.4420.


References
1.
Ray P, Huang B, Tsuji Y . Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5):981-90. PMC: 3454471. DOI: 10.1016/j.cellsig.2012.01.008. View

2.
Liang X, Zhang Z, Lv Y, Tong L, Liu T, Yi H . Reduction of intestinal trimethylamine by probiotics ameliorated lipid metabolic disorders associated with atherosclerosis. Nutrition. 2020; 79-80:110941. DOI: 10.1016/j.nut.2020.110941. View

3.
Spann N, Garmire L, McDonald J, Myers D, Milne S, Shibata N . Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell. 2012; 151(1):138-52. PMC: 3464914. DOI: 10.1016/j.cell.2012.06.054. View

4.
Chen M, Zhu X, Ran L, Lang H, Yi L, Mi M . Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway. J Am Heart Assoc. 2017; 6(9). PMC: 5634285. DOI: 10.1161/JAHA.117.006347. View

5.
Ussher J, Lopaschuk G, Arduini A . Gut microbiota metabolism of L-carnitine and cardiovascular risk. Atherosclerosis. 2013; 231(2):456-61. DOI: 10.1016/j.atherosclerosis.2013.10.013. View