EDN1 and rheumatoid arthritis: Notably, TNF was found to be increased in the serum of lSSc-PAH patients in this study and TNF increases pulmonary vascular resistance [46], stimulates endothelin-1 [47] and leads to PAH in TNF transgenic mice [48] TNF and TNF-regulated genes are increased in patients with rheumatoid arthritis, where TNF inhibition provides a clear therapeutic benefit [49].