Impaired BMPR2 signalling across pulmonary hypertension subgroups: A multicentre exploratory study

Background: Bone morphogenetic protein receptor 2 (BMPR2) signalling is disturbed in heritable pulmonary arterial hypertension (HPAH) patients and blood BMPR2 mRNA expression is reduced. It is unclear, whether BMPR2 expression is altered in other PH patients. Objective: We aimed to investigate the expression of BMPR2 signalling pathway components in different subgroups of PH patients and healthy controls. Methods: In this multicentre, cross-sectional study, a total of 234 subjects were included in seven cohorts: 30 HPAH patients, 38 idiopathic PAH without and 40 idiopathic PAH with comorbidities, 38 systemic sclerosis associated PAH, 47 chronic thromboembolic pulmonary hypertension patients, 9 healthy BMPR2 pathogenic variant carriers and 32 healthy controls. ELISAs and qPCR were performed for BMP10, BMPR2, SMAD5, ID1, EIF2AK4. Univariate ANOVA was used to compare expression across groups, Pearson and Spearman correlation to correlate expression levels with clinical parameters. Results : BMPR2 mRNA expression was significantly reduced in all the PH subgroups compared to healthy controls (p