Melatonin against pulmonary arterial hypertension: is it ready for testing in patients?

Pulmonary arterial hypertension (PAH) is a fatal disease defined as a mean pulmonary artery pressure exceeding 25 mmHg when diagnosed with right heart catheterisation. Its pathophysiology involves multiple molecular pathways, including key components leading to an inflammatory and oxidative stress environment that ultimately causes right ventricular hypertrophy and failure. Compared to the developed world, the overall PAH prevalence is higher in developing countries, including Africa, where it is mostly associated with left heart disease, obstructive/restrictive pulmonary disease, HIV and rheumatic heart disease. Current targeted PAH treatments are expensive, not always available in developing countries, and have a limited impact on PAH progression and mortality rate. Therefore, there is an urgent need for effective and affordable medications that can be used as adjunct therapy against PAH in developing countries. Recently, there have been mounting pre-clinical and clinical data suggesting that melatonin may provide health benefits against PAH.