Activation of ERK signaling by external stimuli such as Endothelin-1 (released by ECs exposed to high pressure) is required for the proliferation of cardiac fibroblasts and their differentiation into myofibroblasts, which deposit excessive amounts of collagen and other ECM components in the heart, contributing to myocardial fibrosis (113, 126). This evidence concerns the gene MAPK1 and Myocardial fibrosis.