Is peroxisome proliferator-activated receptor gamma (PPARγ) a therapeutic target for the treatment of pulmonary hypertension?

Pulmonary hypertension (PH), a progressive disorder associated with significant morbidity and mortality, is caused by complex pathways that culminate in structural and functional alterations of the pulmonary circulation and increases in pulmonary vascular resistance and pressure. Diverse genetic, pathological, or environmental triggers stimulate PH pathogenesis culminating in vasoconstriction, cell proliferation, vascular remodeling, and thrombosis. We conducted a thorough literature review by performing MEDLINE searches via PubMed to identify articles pertaining to PPARγ as a therapeutic target for the treatment of PH. This review examines basic and preclinical studies that explore PPARγ and its ability to regulate PH pathogenesis. Despite the current therapies that target specific pathways in PH pathogenesis, including prostacyclin derivatives, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors, morbidity and mortality related to PH remain unacceptably high, indicating the need for novel therapeutic approaches. Consequently, therapeutic targets that simultaneously regulate multiple pathways involved in PH pathogenesis have gained attention. This review focuses on peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. While the PPARγ receptor is best known as a master regulator of lipid and glucose metabolism, a growing body of literature demonstrates that activation of PPARγ exerts antiproliferative, antithrombotic, and vasodilatory effects on the vasculature, suggesting its potential efficacy as a PH therapeutic target.