On the other hand, reduction in the expression of AT2R and Mas receptors, the release of growth factors from fibroblasts for the occurrence of fibrosis, and the development of oxidative stress due to activation of mitochondria NADPH oxidase 4 as well as the depression of nuclear factor erythroid-2 activity for the occurrence of Ca2+-overload and activation of calcineurin may be involved in inducing pathological cardiac hypertrophy. Here, NOX4 is linked to cardiac hypertrophy.