TY - JOUR
T1 - Role of Pleiotropic Properties of Peroxisome Proliferator-Activated Receptors in the Heart
T2 - Focus on the Nonmetabolic Effects in Cardiac Protection
AU - Barlaka, Eleftheria
AU - Galatou, Eleftheria
AU - Mellidis, Kyriakos
AU - Ravingerova, Tanya
AU - Lazou, Antigone
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Cardiac disorders
KW - Inflammation
KW - Nonmetabolic
KW - Nuclear receptors
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84953790982&partnerID=8YFLogxK
U2 - 10.1111/1755-5922.12166
DO - 10.1111/1755-5922.12166
M3 - Article
C2 - 26589375
AN - SCOPUS:84953790982
SN - 1755-5914
VL - 34
SP - 37
EP - 48
JO - Cardiovascular Therapeutics
JF - Cardiovascular Therapeutics
IS - 1
ER -