In the study of Xin Yi Chan (Chan et al., 2021), gain-of-function mutation of EPAS1 in SMCs increases the expression of fibrillin-1, fibronectin, and elastic fiber components elastin (ELN) via activating endothelin 1 (EDN1) transcription, which contributes to the contractility and stiffness of SMCs and development of pulmonary hypertension in mice. Here, EPAS1 is linked to pulmonary hypertension.