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Professor Nick Morrell, Dr Paul Upton, Dr Amer Rana, and others have identified a novel pathway for the treatment of pulmonary arterial hypertension (PAH) - a debilitating illness that affects the blood vessels in the lungs and often leads to death from heart failure.

Mutations in the BMPR2 gene encoding the bone morphogenetic protein type II receptor (BMPR-II) underlie 70% of heritable PAH cases. Although inflammation promotes PAH, it is unclear how inflammation and BMPR-II protein dysfunction interact to cause disease.

The current study shows that tumour necrosis factor-α (TNFα), a key mediator of inflammation, promotes the development of PAH by:

  • reducing BMPR2 expression
  • promoting BMPR-II cleavage in vascular cells, and
  • driving inappropriate proliferation of smooth muscle cells in pulmonary arteries.

Using anti-TNFα immunotherapy reversed PAH progression in rats. This exciting work provides a rationale for testing anti-TNFα strategies as PAH treatments.

The publication can be read on Nature Communications.

 

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