Pulmonary arterial hypertension and targeting pulmonary vascular remodelling: are we there yet?

Extract Pulmonary arterial hypertension (PAH) is a rare, progressive disorder of the pre-capillary pulmonary circulation, characterised by progressive pulmonary vascular remodelling and vasoconstriction, increased pulmonary vascular resistance, right ventricular hypertrophy, right heart failure and premature death, despite the development of several effective therapies [1–3]. Several factors have been implicated in the pulmonary vascular remodelling, including inflammatory, immunological, epigenetic and genetic factors, such as bone morphogenetic protein receptor type 2 (BMPR2) genetic variants, the most prevalent genetic variant identified in hereditable PAH [4]. Strong associations have been identified between the development of PAH, and 1) aberrant bone morphogenetic protein (BMP) signalling via BMPR2 receptors, 2) dysregulated growth factors, manifesting an imbalance in proliferative and anti-proliferative transforming growth factor (TGF)-β signalling and upregulation of the activin pathway regulated by ActRIIA, 3) progressive endothelial cell dysfunction, 4) pathological distal fibro-proliferation, and 5) plexogenic pulmonary vascular remodelling [4, 5].