Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) signalling is implicated in pulmonary arterial hypertension (PAH). This study identified tacrolimus as an inhibitor of BMPR2 signalling, which bound FK-binding protein 12 (a repressor of BMP signalling) and also inhibited calcineurin. In pulmonary arterial cells from patients with idiopathic PAH, low doses (non-immunosupressive) of tacrolimus reversed dysfunctional BMPR2 signalling. The drug also reversed disease in a mouse model of PAH and in a rat model of progressive severe disease, suggesting that low-dose tacrolimus — which is used to prevent transplant rejection — could be useful in the treatment of PAH.
References
Spiekerkoetter, E. et al. FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J. Clin. Invest. 123, 3600–3613 (2013)
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Charlotte, H. Tacrolimus shows promise in PAH models. Nat Rev Drug Discov 12, 666 (2013). https://doi.org/10.1038/nrd4117
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DOI: https://doi.org/10.1038/nrd4117
