Together, hyperglycemia, ROS, and TNFα, and NF-κB induce cardiac hypertrophy and fibrosis by activating the fibroblasts and the TGF-β1/Smad2/3 signaling (Fiordelisi et al., 2019, Russo and Frangogiannis, 2016). Here, SMAD2 is linked to cardiac hypertrophy.