Article Abstract

Putting skin in the game: dermis-derived stem cells provide insight into familial pulmonary hypertension

Authors: James P. Maloney


Pulmonary arterial hypertension (PAH) is a lethal disease characterized by pulmonary vascular remodeling due to smooth muscle hypertrophy, endothelial proliferation, and adventitial fibrosis. This remodeling progressively obliterates a large cross section of the lung vasculature, turning the normal low pressure pulmonary circulation into a hypertensive circuit and eventually leading to pump failure of the right ventricle. In the past 20 years, multiple effective therapies for PAH have been validated in clinical trials and these drugs have dramatically improved the quality of life of PAH patients. Yet drugs that halt or reverse vascular remodeling have remained elusive and many treated subjects still die (1). Like many seemingly sporadic diseases a subset of PAH is inherited (familial PAH, or FPAH) which enabled the discovery in 2000 via positional cloning that haplo-insufficiency of BMPR2 is the genetic basis of FPAH (2). BMPR2 is a receptor within the TGF-β superfamily. Subsequently, sporadic BMPR2 mutations were also found in a minority of non-familial (idiopathic) PAH patients (3).