In the case of chronic hemodynamic overload, the NOX4 expression level in cardiomyocytes and endothelial cells increases, enhancing HIF-1 and VEGF signaling, activating oxidative stress, causing myocardial fibrosis and vascular proliferation, increasing myocardial capillary density, and acting as a partial myocardial compensation but leading to the development of myocardial remodeling (66). This evidence concerns the gene NOX4 and Myocardial fibrosis.