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BMP9 and pulmonary arterial hypertension

Researchers in our laboratory [collaboratiion] show that blocking the BMP9 signaling pathway reduces the development of pulmonary hypertension in different preclinical models.

Published on 5 March 2019
Pulmonary arterial hypertension (PAH) is a hemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure greater than 25 mmHg at rest. It is a rare disease (15 to 25 cases per one million adults), with a 5-year survival rate of 59% in absence of treatment. Since 2000, mutations in the BMPR2 (Bone Morphogenetic Protein Receptor type 2) gene have been identified as genetic factors predisposing to the development of PAH.

In 2008, we identified BMP9 as a high affinity ligand for the BMPR2 receptor [1] and very recently, mutations in the gene coding for BMP9 were identified in patients with PAH. The question arose as to what is the role of BMP9 in the development of PAH?

In collaboration with researchers from the "Hypertension, physiology and therapeutic innovation" laboratory at Plessis-Robinson, we show [2] that, contrary to what could be expected, blocking the BMP9 signaling pathway through three different approaches reduces the development of pulmonary hypertension in different preclinical models. The proposed mechanism is that BMP9 is a vasoconstrictor agent, the absence of which would therefore cause vasodilation, explaining the protection observed against PAH. In agreement with this hypothesis, the only current therapeutic treatments for this disease are vasodilators.

This discovery offers new insights into the complexity of the processes involved in PAH and shows that additional experiments are needed to understand the function of the BMP signaling pathway in the development of this pathology.

Collaboration with the UMR_S 999, Marie Lannelongue Hospital, Le Plessis-Robinson
* The three approaches are: inactivated mice for Bmp9, anti-BMP9 neutralizing antibody and injection of the extracellular domain of the ALK1 receptor, trapping BMP9.
* In the mechanism proposed by the authors, BMP9 would regulate the expression of endothelin-1, apelin and adrenomedullin.

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