Research ArticlePulmonary Arterial Hypertension

PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation

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Science Translational Medicine  25 Apr 2018:
Vol. 10, Issue 438, eaao0303
DOI: 10.1126/scitranslmed.aao0303

PPARsing the role of lipid metabolism in PAH

During pulmonary hypertension, maladaptive right ventricular hypertrophy, altered mitochondrial metabolism, and occlusive pulmonary vascular remodeling can ultimately lead to heart failure. Here, Legchenko et al. show that activation of the peroxisome proliferator–activated receptor γ (PPARγ) via pioglitazone treatment protects against heart failure in the Sugen hypoxia rat model of pulmonary arterial hypertension. The differential expression of microRNAs in lung tissue and pulmonary vessels from patients with idiopathic pulmonary arterial hypertension was mirrored in the rodent model of heart failure, and cardiac lipid metabolism, genetic, and epigenetic changes associated with PAH were reversed with pioglitazone in the rodents. These findings suggest that targeting PPARγ activation to restore fatty acid oxidation could be therapeutic for pulmonary hypertension and other diseases with altered lipid metabolism.

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