Finding the needle in the haystack: BMP9 and 10 emerge from the genome in pulmonary arterial hypertension

Evidence is emerging for a circulating axis of vascular protection, in which the release of bone morphogenetic proteins (BMPs) 9 and 10 from the liver and right atrium, respectively, provides tonic quiescent signals to the vascular endothelium [1]. These ligands circulate in the plasma at physiologically active concentrations to stimulate BMP signalling in endothelial cells via a receptor complex comprising the activin receptor-like kinase 1 (ALK1; also known as ACVRL1) and the bone morphogenetic protein receptor type 2 (BMPR2) [2]. We now know that the ALK1/BMPR2 receptor complex, expressed almost exclusively on endothelial cells, responds to BMP9 and BMP10 with high affinity (half-maximal effective concentration (EC50) 50–100 pg·mL–1), but does not bind other BMPs [3, 4]. It is well established that heterozygous mutations in the gene encoding BMPR2 are the major genetic cause of pulmonary arterial hypertension (PAH) [5]. In addition, heterozygous mutations in ALK1 are known to be causal in rare cases of PAH, although more commonly cause hereditary haemorrhagic telangiectasia [6].
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Pulmonary vascular disease Editorials Source Type: research