TMAO activates signaling pathways such as TGF-β1/Smad3 and p65 NF-κΒ, leading to a decrease in energy metabolism and mitochondrial function, and impairs the tricarboxylic acid (TCA) cycle, ultimately adversely affecting myocardial contractile function and intracellular calcium processing, and consequently triggering cardiac hypertrophy and myocardial fibrosis [1,20,22]. Here, SMAD3 is linked to cardiac hypertrophy.