Hypertrophic stimuli such as AT-II, ET-1, cytokines, catecholamines, and biomechanical stress may also contribute to detrimental ROS formation in cardiomyocytes, and additional autophosphorylation of ERK1/2 has been reported to trigger pathological ERK1/2-mediated cardiac hypertrophy (Figure 2) [250,251]. Here, EDN1 is linked to cardiac hypertrophy.