Activin A in particular appears to play a substantial pathogenic role: it is upregulated by ECs in PAH lung tissues, can perturb EC function in culture, causes BMPRII downregulation, and when overexpressed selectively in mouse ECs can cause PAH-like disease featuring muscularized pulmonary arteries and right heart hypertrophy (68). Here, BMPR2 is linked to pulmonary arterial hypertension.