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.
Finck
Brian N
BN
Center for Human Nutrition and Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, MO 63110, USA. bfinck@im.wustl.edu
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism*; D004734:Energy Metabolism; D006333:Heart Failure / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors