† These authors contributed equally.
Academic Editor: Gianluca Rigatelli
As a potential causative factor in various cardiovascular diseases, the gut microbe-generated metabolite trimethylamine N-oxide (TMAO) has courted considerable research interest as a potential biomarker. TMAO is a small molecule considered to be beneficial for the health of deep-water animals due to its ability to protect proteins against hydrostatic pressure stress. However, it may cause deleterious effects in humans as mounting evidence suggests that TMAO may enhance atherosclerosis, independent of traditional risk factors. This may be mediated by its capacity to enhance inflammation, platelet activation and thrombosis, and inhibit reverse cholesterol transport. In humans, circulating levels of TMAO have been found to be associated with increased risk of developing atherosclerotic diseases such as carotid atherosclerosis, coronary atherosclerotic heart disease, stroke, and peripheral arteriosclerosis. This review aims to discuss the current role of TMAO in the atherosclerosis process, using animal models and clinical studies, with special attention to determining whether TMAO could be used as a marker for monitoring severity and prognosis in atherosclerosis and to evaluate evidence for its role as a mediator in the pathogenesis of atherosclerotic vascular disease.