TGFB1 and Myocardial fibrosis: It is present in humans in reduced (copper I or Cu+) and oxidised (copper II or Cu2+) forms.25 Unbound/loosely bound tissue copper II ions are powerful catalysts of ROS and oxidative stress and inhibitors of enzymatic antioxidants such as extracellular superoxide dismutase.26 ROS and enhanced oxidative stress damage mitochondrial structure and function, interrupting energy metabolism, activate TGF-β and other profibrotic mediators leading to myocardial fibrosis, and stimulate cardiomyocyte hypertrophy.