Other potential indirect proofs of a direct endothelial damage mediated by these functional antibodies derives from the current therapeutical approaches of severe vascular damage in SSc such as digital ulcers or scleroderma renal crisis which rely on endothelin receptor blockers (i.e., bosentan) or angiotensin converting enzyme (ACE) inhibitors such as captopril [54,55,56]. The gene discussed is ACE; the disease is systemic sclerosis.