SMAD2 and Myocardial fibrosis: Previous studies have suggested that irisin could be a promising therapy against myocardial fibrosis as irisin attenuates angiotensin II-induced cardiac fibrosis via the Nrf2 mediated inhibition of the ROS/TGFβ1/Smad3/Smad2 (Smad2/3) signaling axis [89].