Targeting BMPER as a therapeutic strategy for pulmonary arterial hypertension

Pulmonary arterial hypertension is a life-threatening condition marked by pulmonary vascular remodeling, leading to increased pulmonary artery pressure and right heart hypertrophy. This chronic process involves excessive proliferation and migration of endothelial and smooth muscle cells. Our research, involving both pulmonary arterial hypertension patients and animal models, reveals reduced BMPER levels in cases of pulmonary arterial hypertension. In vitro mechanistic studies are performed using human pulmonary artery endothelial cells and smooth muscle cells. Additionally, we demonstrate BMPER function in vivo through its overexpression via an adeno-associated virus. Our findings indicate that BMPER can attenuate cell proliferation and migration in endothelial cells by inhibiting the PI3K/AKT signaling pathway. Additionally, BMPER reduces smooth muscle cell proliferation and migration by inhibiting BMP4 activity through a paracrine mechanism. Furthermore, BMPER expression is regulated by the transcription factor ERG. Notably, in vivo overexpression of BMPER significantly alleviates the progression of pulmonary arterial hypertension. In summary, our study identifies BMPER as a novel therapeutic target for pulmonary arterial hypertension and provides new insights into the underlying mechanisms of the disease.