Table 2.

Main Pathophysiological Mechanisms of TMAO in AF: Directly and Indirectly

Authors (Year)	Experimental Conditions	Major Findings	References
Yu et al (2018)	Canines	TMAO increased neural activity and the susceptibility of atrial to AF through the p65 NF-κB signaling pathway resulting in the expression of inflammatory cytokines	[35]
Li et al (2019)	Mice	TMAO induces cardiac hypertrophy and fibrosis via the Smad3 signaling pathway	[57]
Wang et al (2020)	Mice	DMB attenuated cardiac structural and electrical remodeling by reducing plasma TMAO concentrations, which negatively regulated the TGF-b1/Smad3 and p65 NF-kB signaling pathways.	[56]
Organ et al (2016)	Mice	Supplementing choline or TMAO significantly increased the severity of heart failure in mice.	[64]
Li et al (2019)	Mice	TMAO aggravated DOX-induced mouse cardiac fibrosis via activation of the NLRP3 inflammasome	[38]
Ke et al (2018)	Human	Elevated circulating TMAO during the aging process may deteriorate endothelial cell senescence and vascular aging through the repression of SIRT1 expression and increased oxidative stress, and the activation of the p53/p21/Rb pathway.	[39]