EDN1 and heart failure: In particular, the Fos–AP-1 pathway transcriptionally stimulates the synthesis of ET-1 and the deposition of collagen (type I, type IV collagens), fibronectin and TGF-β, thereby causing changes in the extracellular matrix that alter cardiac cell proliferation and function, ultimately leading to cardiomyocyte hypertrophy and heart failure (Pan et al., 2012; Wang et al., 2009; Avouac et al., 2012).