Is pulmonary vascular disease reversible with PPAR ? agonists?

Severe angio-obliterative PAH remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio-obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another. PPARs, especially the isoform, are largely expressed in pulmonary artery endothelial cells and smooth muscle cells. They are also found on endothelial progenitor cells. Several previous studies have highlighted the role of PPAR agonists in reversal of vascular remodeling especially in coronary, carotid and peripheral vascular disease atherosclerotic plaques. Experimental studies have also revealed that PPAR activation affects many different pathways; thus, the effect of PPAR is multifaceted, affecting almost every pathobiological pathway involved in the development of PAH simultaneously. We thereby hypothesize that PPAR agonists may play a key role in reversing severe pulmonary angio-obliterative changes and promote microvascular regeneration which may substitute the need for heart-lung transplantation in such patients.