TY - JOUR
T1 - The role of PPAR in myocardial response to ischemia in normal and diseased heart
AU - Ravingerova, Tana
AU - Adameova, Adriana
AU - Carnicka, Slavka
AU - Nemcekova, Martina
AU - Kelly, Tara
AU - Matejikova, Jana
AU - Galatou, Eleftheria
AU - Barlaka, Eleftheria
AU - Lazou, Antigone
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Cardioprotection
KW - HMG-CoA reductase inhibitors
KW - Hypolipidemic drugs
KW - Myocardial ischemia
KW - Peroxisome proliferator-activated receptors
KW - Pleiotropic effects
UR - http://www.scopus.com/inward/record.url?scp=83155173464&partnerID=8YFLogxK
U2 - 10.4149/gpb_2011_04_329
DO - 10.4149/gpb_2011_04_329
M3 - Review article
C2 - 22131314
AN - SCOPUS:83155173464
SN - 0231-5882
VL - 30
SP - 329
EP - 341
JO - General Physiology and Biophysics
JF - General Physiology and Biophysics
IS - 4
ER -
