Introduction: Pulmonary hypertension (PH), especially Group 3 (chronic lung disease-associated) PH, is a severe condition with high mortality. Mutations in the bone morphogenic protein (BMP) pathway have been recognized as risk factors for pulmonary arterial hypertension-PH (Group 1 PH). Our recent research identified the protein BMPER (BMP endothelial cell precursor-derived regulator), a regulator of vascular development, as a novel contributor to vascular remodeling of pulmonary arterial hypertension. However, BMPER’s roles in Group 3 PH remain unknown. This study aims to unearth BMPER’s role in the mechanisms of Group 3 PH vasculopathy.
Methods: To understand the role of BMPER in Group 3 PH, we evaluated BMPER protein expression in idiopathic pulmonary fibrosis (IPF) PH patient serum and lung explant samples. Next, we examined BMPER cellular distribution in these lung sections using immunostaining.
Results: BMPER Expression: BMPER levels demonstrated a 4.5-fold increase in IPF-PH patient lungs, compared to non-PH control samples. However, no significant difference was observed with PH serum compared to control samples (1.03 +/- 0.13 vs 1.00 +/- 0.08). These results suggest that local BMPER levels in lung might be upregulated during the development of PH. BMPER distribution: BMPER was highly enriched in the intima and media of arterioles and advanced lesions of IPF-PH lungs, compared to non-PH control lungs, indicated by the co-localization of BMPER and vascular endothelial cell marker, lectin, or smooth muscle cell (SMC) marker, alpha-SMC-actin.
Conclusions: These findings suggest that BMPER might play a key role in vasculopathy and vascular remodeling in pulmonary hypertension due to chronic lung disease. We propose that therapies targeting BMPER activation/upregulation may attenuate the development of Group 3 (IPF) PH and lead to novel therapeutic options and ultimately, improve the quality of life for patients.
