Bone Morphogenetic Protein Signaling in Pulmonary Arterial Hypertension

Abstract

A wealth of evidence from human genetics, developmental and cell biology, and translational science has implicated members of the bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β ) signaling family in the pathogenesis of pulmonary arterial hypertension (PAH). The discovery of loss-offunction germline mutations in BMPR2 and in functionally related BMP/TGF-β signal transduction molecules as causes of heritable PAH and several overlapping congenital vascular syndromes has catalyzed work to elucidate how BMP signals critically regulate vascular development, vascular homeostasis, inflammation, metabolism and pathogenic remodeling. This work in vascular biology and experimental medicine has in turn led to a more nuanced understanding by which the structurally diverse family of BMP ligands and receptors achieve their tissue-specific and context-dependent functions. Recently this work has shed light on promising new strategies by which dysregulated BMP/TGF-β might be modulated for therapeutic benefit in PAH and related conditions. BMP Signaling in the Cardiopulmonary SystemBMP signaling plays a fundamental role in the development and homeostasis of the heart and the systemic and pulmonary circulation. Spatiotemporal specificity of BMP signaling in the cardiopulmonary system is achieved by selective expression