Abstract 20431: Portopulmonary Hypertension is Marked by Severely Diminished Circulating Bone Morphogenetic Protein 9

Abstract Background: Defects in bone morphogenetic protein (BMP) signaling contribute to the pathogenesis of pulmonary arterial hypertension (PAH). BMP9 is a circulating vascular endothelial quiescence factor with protective effects in PAH. We hypothesized that diminished BMP9 signaling may contribute to PAH. Methods and Results: Circulating levels of BMP9 and its circulating antagonist soluble Endoglin (sEng) were measured in 215 patients with WHO Group 1 PAH, Group 2 or Group 3 pulmonary hypertension, and 63 healthy individuals using a sensitive immunoassay. BMP9 was minimally decreased among patients with Group 1 PAH as a whole (187 ± 9 pg/mL vs. 218 ± 10 pg/mL in healthy controls, mean ± SEM, n=174, p=0.0026), but was profoundly decreased among patients with portopulmonary hypertension (PoPH, 76 ± 9 pg/mL, n=37, pu003c0.0001), segregating PoPH from all other etiologies of PAH (ROC-AUC=0.91 ± 0.03, pu003c0.0001). BMP9 levels were significantly lower in PoPH vs. patients with liver disease without PAH (218 ± 19...