Table 3.

Summary of studies about mechanisms of TMAO contributing to HF by time.

Source	Year	Species	Level	Pathway	Effect
Organ et al. [51]	2016	C57BL6/J mice	Organ/system	—	Leads to pulmonary edema, enlargement of heart, increased BNP, decreased left ventricular ejection fraction and myocardial fibrosis
Seldin et al. [52]	2016	Human endothelial cells, LDLR (−/−) mice	Molecule and gene	NF‐κB pathway	Elevated inflammatory gene expression in mice, promotes recruitment of activated leukocytes to endothelial cells
Sun et al. [53]	2016	Human umbilical vein endothelial cells	Molecule	—	Induces inflammation and endothelial dysfunction through ROS‐TXNIP‐NLRP3 inflammasome activation
Chen et al. [54]	2017	Human umbilical vein endothelial cells, aortas from ApoE−/− mice	Molecule	SIRT3–SOD2–mitochondrial ROS signaling pathway (inhibition)	Boosts vascular inflammation through NLRP3 inflammasome activation
Makrecka‐Kuka et al. [55]	2017	ICR mice	Organ/system	—	Impairs β‐oxidation in cardiac mitochondria, promotes cardiac energy metabolism disturbances, and decreases pyruvate metabolism by impairing substrate flux
Li et al. [56]	2019	Sprague‐Dawley rats	Molecule	Smad3 pathway	Promotes myocardial hypertrophy and fibrosis
Brunt et al. [57]	2020	Human and mice	Organ/system	—	Promotes age‐related vascular oxidative stress and endothelial dysfunction
Yoshida et al. [58]	2022	Mice	Molecule	—	Induces decrease of phosphocreatine and ATP levels in heart tissue by suppressing mitochondrial complex IV activity

Abbreviations: ATP, adenosine triphosphate; BNP, brain natriuretic peptide; LVEF, left ventricular ejection fraction.