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© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Nature reviews | Cardiology activation of peroxisome proliferator-activated receptor-γ (PParγ) with pioglitazone reverses metabolic changes that occur with pulmonary arterial hypertension (PaH). these findings reveal a potential therapy to prevent the development of right ventricular failure, which is the leading cause of death in patients with PaH. PParγ is an important metabolic regulator in vascular cells, but its role in the heart is uncertain. investigators now show that deletion of Pparg, which encodes PParγ, specifically in cardiomyocytes of mice led to biventricular systolic dysfunction and intramyocellular lipid accumulation. in a rat model of severe PaH, oral treatment with the PParγ agonist pioglitazone completely reversed the PaH and vascular remodelling and prevented the development of right ventricular failure. the cardiomyocyte lipotoxicity and mitochondrial disarray observed in the rat model of PaH were prevented by pioglitazone. a series of microrNa (mirNa) arrays, mrNa sequencing, and lipid metabolism studies revealed dysregulation of cardiac hypertrophy, myocardial contractility, fibrosis, and fatty acid transport and oxidation. in particular, pre-mir-197 and pre-mir-146b were upregulated in the right ventricles of rats with PaH. these mirNas repress genes (Cpt1b and Fabp4) that drive fatty acid oxidation in cardiomyocytes, and were downregulated with pioglitazone. Of note, levels of these mirNas were also upregulated in the pressure-overloaded right ventricles of patients with end-stage PaH. “PParγ activation can normalize epigenetic and transcriptional regulation primarily related to disturbed lipid metabolism and mitochondrial morphology [and] function in the failing right ventricle and the hypertensive pulmonary vasculature, representing a therapeutic approach for PaH,” conclude the researchers. Gregory B. Lim P U L M O N A R Y H Y P E R T E N S I O N