Does Sotatercept attenuate pulmonary vascular remodeling and right ventricular dysfunction in preclinical models of PAH?
Sotatercept acts as a disease-modifying therapy in PAH by restoring SIN3a expression and rebalancing BMPR2/TGF-β signaling to attenuate vascular remodeling and right ventricular dysfunction.
SIN3a is a central epigenetic regulator of PASMC homeostasis that integrates oxidative stress, inflammation, and fibrotic signaling. Loss of SIN3a accelerates PAH progression, whereas Sotatercept restores SIN3a expression, rebalances BMPR2 and TGF-β signaling, and attenuates pulmonary vascular remodeling and right ventricular dysfunction. Together, these findings identify SIN3a as a disease-relevant therapeutic target and support the use of Sotatercept as a disease-modifying approach for pulmonary vascular disease.
Jankowski et al. (Tue,) studied this question.