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: Tana Ravingerova, Adriana Adameova, Slavka Carnicka, Martina Nemcekova, Tara Kelly, Jana Matejikova, Eleftheria Galatou, Eleftheria Barlaka, Antigone Lazou
• Journal: General physiology and biophysics (Gen Physiol Biophys) Vol. 30 Issue 4 Pg. 329-41 (Dec 2011) ISSN: 0231-5882 [Print] Slovakia
• PMID: 22131314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cardiotonic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Ligands
• Peroxisome Proliferator-Activated Receptors

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Diabetes Complications (metabolism)
• Heart (physiology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Inflammation
• Ligands
• Models, Biological
• Myocardial Ischemia (metabolism, pathology)
• Peroxisome Proliferator-Activated Receptors (metabolism, physiology)
• Reperfusion Injury (metabolism)
• Tissue Distribution
• Transcriptional Activation