Why the study?
Bmpr2 mutations are critical risk factors for hereditary PAH, but only about 20% of carriers develop disease. How environmental factors like inflammation trigger susceptibility in Bmpr2 mutants remains an unmet medical need.
Population
Monoallelic Bmpr2 mutant rats, wild-type littermates, Bmpr2-mutant hereditary PAH patient samples, and endothelial cells
Comparison
Second hit exposures (5-LO adenovirus, monocrotaline, SU5416, hypoxia) vs controls
Design
Preclinical animal and in vitro translational study
Follow-up
Up to 1 year
Authors
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May link 5-LO inflammation to PAH susceptibility in Bmpr2 carriers; leaves open whether pathway inhibition prevents disease.
In a 2-hit model, 5-LO-mediated lung inflammation synergizes with phenotypically silent Bmpr2 mutations to induce severe PAH and neointimal transformation via TGF-β signaling.
Tian et al. (2019) studied this question.