One study [50] showed that endothelial cell-derived ET-1 promotes cardiac fibrosis and heart failure in diabetic hearts through stimulation of EndoMT, and a more recent study employing immunopurified CD31+ dermal endothelial cells from SSc patients showed that TGF-β and ET-1 induced EndoMT in normal and SSc endothelial cells, that these effects involved the Smad pathway, and that they were blocked by the specific ET-1 receptor antagonist, macitentan [26]. Here, EDN1 is linked to heart failure.