Abstract
BACKGROUND: Congenital pulmonary artery hypertension (PAH) has been clinically correlated in 70-80% of cases with mutations at the bone morphogenetic protein receptor 2 (BMPR2) genetic site. However, there is also clinical and basic science/laboratory literature indicating a dose-response relationship between BMP signaling and the evolution of PAH (e.g., increased endothelial, smooth muscle, and progenitor cell production, with calcifications). METHODS: Clinical PAH, characterized by pulmonary artery remodeling, elevated right ventricular pressures, increased vascular constriction, and inflammation, is largely due to congenital mutations at the BMPR2 site. Both clinical and laboratory studies have confirmed the correlation between dysfunction at the BMPR2 genetic site and PAH. However, additional basic science and clinical studies suggest a dose-response relationship between BMP signaling and the evolution of PAH. RESULTS: Laboratory studies found that pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions proliferated in response to BMP-2 in a dose-dependent fashion. Others noted that PASMCs extracted from patients with Primary Pulmonary Hypertension (PPH) demonstrated abnormal growth responses to transforming growth factor-beta (TGF-β) in a dose-related manner. CONCLUSIONS: The clinical/basic science literature appears to document a dose-dependent relationship between BMP and PAH (independent of the congenital lesions). Does this mean patients undergoing lumbar fusions with BMP are at risk for PAH?