Therefore, the mechanistic contribution of EndMT to the pathogenesis of SSc vasculopathy is postulated to involve a synergistic and complex activation of a large variety of endothelial cell types from different body districts exposed to multiple local biological mediators, particularly TGF-β, but also IL-1β, TNF-α, PDGF, VEGF, and endothelin-1 (ET-1) (17, 18, 77, 78, 112, 114, 116–119). This evidence concerns the gene EDN1 and vascular disorder.