Although the detrimental effects of ET-1 are mostly mediated via ETAR, ETBR may play a part in the pathophysiological event of cardiac fibrosis since ETBRs were detected to be upregulated in fibrotic-related diseases such as scleroderma-associated fibrotic lung disease [41] and pulmonary arterial hypertension [42]. This evidence concerns the gene EDN1 and scleroderma.