Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics.
Meyammai ShanmughamSophie BellangerChen Huei LeoPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Trimethylamine N-oxide (TMAO) is a biologically active gut microbiome-derived dietary metabolite. Recent studies have shown that high circulating plasma TMAO levels are closely associated with diseases such as atherosclerosis and hypertension, and metabolic disorders such as diabetes and hyperlipidemia, contributing to endothelial dysfunction. There is a growing interest to understand the mechanisms underlying TMAO-induced endothelial dysfunction in cardio-metabolic diseases. Endothelial dysfunction mediated by TMAO is mainly driven by inflammation and oxidative stress, which includes: (1) activation of foam cells; (2) upregulation of cytokines and adhesion molecules; (3) increased production of reactive oxygen species (ROS); (4) platelet hyperreactivity; and (5) reduced vascular tone. In this review, we summarize the potential roles of TMAO in inducing endothelial dysfunction and the mechanisms leading to the pathogenesis and progression of associated disease conditions. We also discuss the potential therapeutic strategies for the treatment of TMAO-induced endothelial dysfunction in cardio-metabolic diseases.
Keyphrases
- oxidative stress
- diabetic rats
- reactive oxygen species
- induced apoptosis
- cardiovascular disease
- high glucose
- type diabetes
- human health
- small molecule
- poor prognosis
- risk assessment
- drug induced
- cell death
- endoplasmic reticulum stress
- high fat diet
- adipose tissue
- endothelial cells
- glycemic control
- heat shock protein
- case control