The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension

Global Cardiology Science & Practice
Mark L OrmistonNicholas W Morrell

Abstract

Human genetic discoveries offer a powerful method to implicate pathways of major importance to disease pathobiology and hence provide targets for pharmacological intervention. The genetics of pulmonary arterial hypertension (PAH) strongly implicates loss-of-function of the bone morphogenetic protein type II receptor (BMPR-II) signalling pathway and moreover implicates the endothelial cell as a central cell type involved in disease initiation. We and others have described several approaches to restore BMPR-II function in genetic and non-genetic forms of PAH. Of these, supplementation of endothelial BMP9/10 signalling with exogenous recombinant ligand has been shown to hold considerable promise as a novel large molecule biopharmaceutical therapy. Here, we describe the mechanism of action and discuss potential additional effects of BMP ligand therapy.

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Citations

Jan 25, 2016·Cytokine & Growth Factor Reviews·Christian HiepenPetra Knaus
Dec 22, 2016·Expert Opinion on Therapeutic Targets·Christophe GuignabertMarc Humbert
Aug 17, 2016·Biochemical Society Transactions·Wei LiNicholas W Morrell
Aug 14, 2019·Nature Reviews. Cardiology·Laura SouthgateNicholas W Morrell
Apr 28, 2017·Cellular and Molecular Life Sciences : CMLS·Mar OrriolsPeter Ten Dijke
Oct 23, 2020·Cytokine & Growth Factor Reviews·Erik Martinez-HackertToril Holien
Jun 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yicheng YangChangming Xiong

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