SMAD2 and cardiac hypertrophy: These cells produce various proinflammatory cytokines and ROS that activates multiple signaling pathways (CaNA/STAT3, TGF-β1/Smad2/3, IKKɑ/NF-kB, and NOX1/4), thereby leading to cardiac hypertrophy, fibrosis, inflammation and DNA damage (cardiac remodeling).