Using pneumonectomy combined with monocrotaline (PNT/MCT) as a severe PAH model in rats, we found that combination therapies using aerosolized AAV1.hSERCA2a with a potent STAT3 inhibitor (HJC0152) or AAV1.hBMPR2: (1) significantly restored BMPR2 expression in the lungs, (2) attenuated the pulmonary vascular remodeling and resistance, and (3) inhibited RV remodeling and significantly restored RV function. Here, BMPR2 is linked to pulmonary arterial hypertension.