Additionally, functional vascular changes in SSc-RP patients include impaired endothelial-dependent vasodilation, possibly due to increased vasoconstrictor (endothelin-1) [38, 39] and decreased vasodilator (nitric oxide and prostacyclin) production, though variance in these molecules likely relates to disease activity and damage progression [40, 41]. Here, EDN1 is linked to systemic sclerosis.