Skip to Main content Skip to Navigation
Journal articles

Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension.

Abstract : Mutations in the gene encoding bone morphogenetic protein (BMP) receptor type 2 (BMPR-2) have been reported in pulmonary arterial hypertension (PAH), but their functional relevance remains incompletely understood. BMP receptor expression was evaluated in human lungs and in cultured pulmonary artery smooth muscle cells (PASMCs) isolated from 19 idiopathic PAH patients and nine heritable PAH patients with demonstrated BMPR-2 mutations. BMP4-treated PASMCs were assessed for Smad and p38 mitogen-activated protein kinase (MAPK) signalling associated with mitosis and apoptosis. Lung tissue and PASMCs from heritable PAH patients presented with decreased BMPR-2 expression and variable increases in BMPR-1A and BMPR-1B expression, while a less important decreased BMPR-2 expression was observed in PASMCs from idiopathic PAH patients. Heritable PAH PASMCs showed no increased phosphorylation of Smad1/5/8 in the presence of BMP4, which actually activated the p38MAPK pathway. Individual responses varied from one mutation to another. PASMCs from PAH patients presented with an in vitro proliferative pattern, which could be inhibited by BMP4 in idiopathic PAH but not in heritable PAH. PASMCs from idiopathic PAH and more so from heritable PAH presented an inhibition of BMP4-induced apoptosis. Most heterogeneous BMPR-2 mutations are associated with defective Smad signalling compensated for by an activation of p38MAPK signalling, accounting for PASMC proliferation and deficient apoptosis.
Document type :
Journal articles
Complete list of metadata

Cited literature [30 references]  Display  Hide  Download
Contributor : Georges Guellaen <>
Submitted on : Friday, November 20, 2009 - 3:32:09 PM
Last modification on : Wednesday, September 16, 2020 - 5:04:24 PM
Long-term archiving on: : Saturday, November 26, 2016 - 3:26:24 PM


 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document




Laurence Dewachter, Serge Adnot, Christophe Guignabert, Ly Tu, Elisabeth Marcos, et al.. Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension.. European Respiratory Journal, European Respiratory Society, 2009, 34 (5), pp.1100-10. ⟨10.1183/09031936.00183008⟩. ⟨inserm-00433927⟩



Record views