It is well established that EC dysfunction plays a central role in HF development and progression [23], whilst EC paracrine signalling (e.g. NO, prostacyclin, angiotensin II [AngII] and endothelin 1 [ET-1]) is a critical modulator of cardiomyocyte survival, growth and contractility, and cardiac fibroblast function and extracellular matrix (ECM) turnover. This evidence concerns the gene EDN1 and hydrops fetalis.