Bone morphogenetic protein 10 is increased in precapillary pulmonary hypertension patients.

Abstract

Aims: Precapillary pulmonary hypertension (precPH) results in increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults, primarily produced by RA cardiomyocytes. The aim of this study was to investigate BMP10 expression in the right heart and systemic circulation and to identify potential triggers for increased BMP10 secretion associated with precPH.

Methods and results: We examined BMP10 mRNA and protein expressions in RA tissue. Circulating BMP10 plasma levels were determined using ELISA. BMP10 transcriptional activity was studied using a BRE-Luciferase assay. Correlation analyses were performed between circulating BMP10 and RA dilatation as well as right ventricular (RV) function. Finally, we determined the impact of pressure unloading on BMP10 activity in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients before and after pulmonary endarterectomy (PEA).BMP10 mRNA, protein and activity were significantly increased in the precPH right atrium. While circulating BMP10 protein levels were elevated, no significant changes were observed in BMP10 transcriptional activity between precPH and controls. Interestingly, RA dilatation, increased RA pressure, high NTproBNP levels and reduced RV ejection fraction were associated with high BMP10 activity. Finally, pressure unloading after PEA in a cohort of CTEPH patients, resulted in reduced BMP10 activity.

Conclusions: In conclusion, RA BMP10 expression and plasma levels are increased in precPH, likely triggered by excessive RA dilatation and pressure overload. Future studies are needed to determine whether increased BMP10 release is an adaptive mechanism or a potential therapeutic target.