The PPAR regulatory system in cardiac physiology and disease

Myocardial energy metabolism is an important determinant of cardiac structure and function. Modulating metabolism is therefore an attractive therapeutic avenue for the treatment of cardiac disease. The peroxisome proliferator-activated receptor family (PPARalpha, beta/delta, gamma) of nuclear receptor transcription factors is an important regulator of cardiac metabolism and has been targeted for pharmacologic therapies designed to modulate metabolism. The PPARs control myocardial metabolism by transcriptionally regulating genes encoding enzymes involved in fatty acid and glucose utilization. The expression and activity of the PPARs and their coactivator protein PGC-1alpha is dynamically regulated in several cardiomyopathic and metabolic diseases. This review will summarize these findings and other recent studies regarding the effects of experimental PPAR activation and deactivation and its potential impact on cardiomyopathic remodeling.