Given the improvement of several hemodynamic and clinical parameters following PDE5 inhibition, sildenafil, in 2005, and, thereafter, tadalafil have been approved by the US FDA and became first-line therapies for PAH [63], primary or secondary to other connective tissue diseases, such as scleroderma (SSc) or systemic lupus erythematosus (SLE)—which share identical pathological changes in pulmonary vessels [55]. Here, PDE5A is linked to pulmonary arterial hypertension.