We found that that interference with PARP1-PKM2 signaling delivers a combined attack on multiple cell types and multiple detrimental mechanisms underlying pathological RV remodeling in addition to reverse pulmonary artery wall thickening.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: Although the pulmonary vasculature is the locus of the initial insult, short- and long-term outcomes of patients with PAH are dependent largely on their RV function. Here, PARP1 is linked to pulmonary arterial hypertension.