PPARgamma as a potential therapeutic target in pulmonary hypertension

Pulmonary hypertension (PH) is a progressive disorder of the pulmonary circulation associated with significant morbidity and mortality. The pathobiology of PH involves a complex series of derangements causing endothelial dysfunction, vasoconstriction and abnormal proliferation of pulmonary vascular wall cells that lead to increases in pulmonary vascular resistance and pressure. Recent evidence indicates that the ligand-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma) can have a favorable impact on a variety of pathways involved in the pathogenesis of PH. This review summarizes PPARgamma biology and the emerging evidence that therapies designed to activate this receptor may provide novel approaches to the treatment of PH. Mediators of PH that are regulated by PPARgamma are reviewed to provide insights into potential mechanisms underlying therapeutic effects of PPARgamma ligands in PH.