NOX4 and Myocardial fibrosis: They found that chronic myocardial ischemia significantly reduced KLF15 expression, which then increased the transcription of TGF-β1 and Nox4 mRNA, and that sustained TGF-β1/Nox4 signaling led to the production of large amounts of oxidants, which aggravated OS in diseased hearts, as well as myocardial fibrosis and hypertrophy (194).