NOX4 and heart failure: To elucidate whether TGF-β-induced activation of Nox430 in M9, a principal ROS-generating NADPH oxidase31,32 in cardiomyocytes33, is involved in increased DNA damage and the development of heart failure, we injected Nox4-shRNA adeno-associated virus 9 (AAV9) vector to suppress Nox4 expression (Fig. 5a).