PPAR ligands: are they potential agents for cardiovascular disorders?

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPARalpha, PPARgamma, and PPARbeta/delta. Fibrates are acting via PPARalpha, and they are used as lipid-lowering agents. PPARgamma agonists reduce insulin resistance and have been used in the treatment of type 2 diabetes. As the knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including a novel role in the management of cardiovascular disorders (CVD). PPARalpha/gamma dual agonists are currently under development and hold considerable promise in the management of type 2 diabetes and provide an effective therapeutic option for treating the multifactorial components of CVD. Several experimental and clinical evidences elucidated the beneficial effects of PPAR ligands in prevention and treatment of various CVD. However, PPARalpha and PPARgamma agonists have been shown to be proinflammatory and proatherogenic in a few studies. Further, PPARgamma ligands have been noted to be involved in the pathogenesis of congestive heart failure. These controversial results obtained from a few studies created further complication in understanding the role of PPARs. The function of PPARdelta and its potential as a cardiovascular therapeutic target are currently under investigation. The present review focuses on the merits and limitations of PPAR agonists with regard to their use in CVD. Copyright (c) 2007 S. Karger AG, Basel.