Furthermore, endothelin-1 and angiotensin II (a bioactive peptide of the renin–angiotensin system), which are often elevated in SSc, may upregulate mitochondrial ROS generation through the activation of NADPH oxidase (Nozoe et al., 2008; Wosniak et al., 2009; Wen et al., 2012). Here, EDN1 is linked to systemic sclerosis.