title: The role of PPAR in myocardial response to ischemia in normal and diseased heart.
abstract: Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors, belong to the nuclear hormone receptor superfamily regulating expression of genes involved in different aspects of lipid metabolism, inflammation and cardiac energy production. Activation of PPAR-α isoform by its natural ligands, fatty acids (FA) and eicosanoids, promotes mitochondrial FA oxidation as the primary ATP-generating pathway. On the other hand, PPAR-γ regulates lipid anabolism or storage, while, until recently, the function of PPAR-β/δ has been less explored. Under conditions associated with acute or chronic oxygen deprivation, PPAR-α modulates expression of genes that determine substrate switch (FA vs. glucose) aimed at maintenance of basic cardiac function. Although PPAR-α and PPAR-γ synthetic agonists, hypolipidemic and antidiabetic drugs, have been reported to protect the heart against ischemia/reperfusion injury, it is still a matter of debate whether PPAR activation plays a beneficial or detrimental role in myocardial response to ischemia, in particular, in pathological conditions. This article reviews some findings demonstrating the impact of PPAR activation on cardiac resistance to ischemia in normal and pathologically altered heart. Specifically, it addresses the issue of susceptibility to ischemia in the diabetic myocardium, with particular regards to the role of PPAR. Finally, involvement of PPAR in the mechanisms of lipid-independent cardioprotective effects of some hypolipidemic drugs is also discussed.
authors: Institute for Heart Research, Slovak Academy of Sciences, Centre of Excellence NOREG SAS, Bratislava, Slovak Republic. usrdravi@savba.sk
authors: Tana
authors: T
authors: Ravingerova
authors: Adriana
authors: A
authors: Adameova
authors: Slavka
authors: S
authors: Carnicka
authors: Martina
authors: M
authors: Nemcekova
authors: Tara
authors: T
authors: Kelly
authors: Jana
authors: J
authors: Matejikova
authors: Eleftheria
authors: E
authors: Galatou
authors: Eleftheria
authors: E
authors: Barlaka
authors: Antigone
authors: A
authors: Lazou
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D048909:Diabetes Complications / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation; D008024:Ligands; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism; D014018:Tissue Distribution; D015533:Transcriptional Activation
chemical_list: D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors