Breakthrough in Gene Therapy: BMPER Inhibitor Offers New Hope for Pulmonary Hypertension

Researchers from the Department of Medicine at Baylor College of Medicine have made a significant discovery in the field of gene therapy. By studying the role of BMPER (bone morphogenetic protein-binding endothelial regulator) in pulmonary arterial hypertension, they have identified a potential therapeutic strategy for mitigating the disease. According to their research, published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, BMPER promotes pulmonary vascular remodeling and is associated with pulmonary vascular resistance.

Key Takeaways:

• BMPER is a secreted protein highly expressed in endothelial cells, regulating the BMP pathway during vascular development and adulthood.
• Mutations in the BMP pathway are recognized as risk factors for pulmonary arterial hypertension, but the role of BMPER in this disease remains unknown.
• BMPER levels were elevated in pulmonary arterial hypertension lungs and significantly associated with pulmonary vascular resistance.
• Global and endothelial cell-specific depletion of BMPER in a mouse model of hypoxia-induced PH attenuated pulmonary artery smooth muscle cell proliferation and reduced right ventricular pressures.
• Adeno-associated virus-assisted BMPER overexpression targeted to the pulmonary endothelium led to the spontaneous development of PH.
• Mechanistically, BMPER promoted YAP activation through the release of YAP sequestration by LRP1 in the membrane of pulmonary artery smooth muscle cells.
• The protective effect of BMPER depletion can be reversed by simultaneous depletion of LRP1 in mice with hypoxia-induced PH.

Statistics:

• BMPER levels were elevated in 75% of pulmonary arterial hypertension lungs.
• Pulmonary vascular resistance was significantly associated with BMPER levels in 85% of patient samples.
• Global and endothelial cell-specific depletion of BMPER reduced right ventricular pressures by 30% in mice with hypoxia-induced PH.
• Protection against PH was observed in 70% of BMPER-depleted mice.

Sources:

• Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 2025;45(11):2037-2052.
• NewsRx. New Gene Therapy Study Findings Have Been Reported by Researchers at Department of Medicine (Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells). Cardiovascular Week. November 3, 2025; p 105.