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n prostacyclin production and increased cell death of pulmonary microvascular endothelial cells. Conclusions and Relevance This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.Tobacco smoking is a major threat to health. There is no doubt about the need to promote and support cessation at every op