title: Role of Pleiotropic Properties of Peroxisome Proliferator-Activated Receptors in the Heart: Focus on the Nonmetabolic Effects in Cardiac Protection.
abstract: Peroxisome proliferator-activated receptors, PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptors that function as transcriptional regulators of lipid metabolism, energy homeostasis, and inflammation. Given the role of metabolism imbalance under pathological states of the heart, PPARs have emerged as important therapeutic targets, and accumulating evidence highlights their protective role in the improvement of cardiac function under diverse pathological settings. Although the role of PPARs in the regulation of cardiac substrate utilization preference and energy homeostasis is well documented, their effects related to the regulation of cellular inflammatory and redox responses in the heart are less studied. In this review, we provide an overview on recent progress with respect to understanding the role of the nonmetabolic effects of PPARs in cardiac dysfunction, namely during ischemia/reperfusion injury, hypertrophy, and cardiac failure, and highlight the mechanisms underlying the protective effects against inflammation, oxidative stress, and cell death. The role of receptor-independent, nongenomic effects of PPAR agonists is also discussed.
authors.affiliation: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Barlaka
authors.affiliation: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Galatou
authors.affiliation: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Mellidis
authors.affiliation: Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Tanya
authors.initials: T
authors.lastname: Ravingerova
authors.affiliation: School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antigone
authors.initials: A
authors.lastname: Lazou
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015195:Drug Design; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D047492:Peroxisome Proliferator-Activated Receptors
keywords: Cardiac disorders; Inflammation; Nonmetabolic; Nuclear receptors; Oxidative stress