Approaches to treat pulmonary arterial hypertension by targeting BMPR2: from cell membrane to nucleus

Pulmonary arterial hypertension (PAH) is estimated to affect between 10 and 50 people per million worldwide. The lack of cure and devastating nature of the disease means that treatment is crucial to arrest rapid clinical worsening. Current therapies are limited by their focus on inhibiting residual vasoconstriction rather than targeting key regulators of the cellular pathology. Potential disease-modifying therapies may come from research directed towards causal pathways involved in the cellular and molecular mechanisms of disease. It is widely acknowledged that targeting reduced expression of the critical bone morphogenetic protein type-2 receptor and its associated signalling pathways is a compelling therapeutic avenue to explore. In this review, we highlight the advances that have been made in understanding this pathway and the therapeutics that are being tested in clinical trials and the clinic to treat PAH.