Pulmonary arterial hypertension (PAH) is a progressive disease
of the small pulmonary arteries in which patients suffer from
elevated pulmonary arterial pressure, right ventricular failure
and a reduction in gas exchange. Left untreated the median
survival from diagnosis is ~2.8 years, though outcome is
significantly worse if patients have underlying pulmonary
fibrosis or scleroderma. Injury to the endothelium probably
initiates the disease process, with increased production of
vasoconstrictors (endothelin and thromboxane) and growth
factors accompanying the loss of vasodilator and anti-platelet
agents, prostacyclin and nitric oxide, which results in vascular
remodelling. To date prostacyclin therapy still remains the most
efficacious treatment for PAH, although its short half-life and
cumbersome delivery (continuous infusion) meant analogues
with improved stability and alternative routes of delivery were
developed. Classically, prostacyclin agents are thought to
produce haemodynamic and anti-proliferative effects through
prostacyclin (IP) receptors coupled to cyclic AMP generation,
though other prostanoid receptors may contribute (EP2, EP4) or
counterbalance (EP1, EP3) these responses. Increasing evidence
suggests peroxisome proliferator-activated receptors (PPARs)
are also cellular targets for prostacyclin agonists, regulating
cell growth, inflammation and apoptosis through these
transcription factors. Activation involves ligand binding and/or
membrane receptors but probably not cyclic AMP. Here we
discuss recent advances in our understanding of PPARs and
how they may represent an important therapeutic target in PA
