PPARs and Myocardial Response to Ischemia in Normal and Diseased Heart
| Autor: | Nemčeková M, Adriana Adameova, Tana Ravingerova, Antigone Lazou, S Carnicka, Jana Matejikova, Tara Kelly |
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| Rok vydání: | 2011 |
| Předmět: |
Cardioprotection
chemistry.chemical_classification medicine.medical_specialty Ischemia Peroxisome proliferator-activated receptor Inflammation Lipid metabolism Biology medicine.disease Endocrinology Nuclear receptor chemistry Internal medicine medicine lipids (amino acids peptides and proteins) medicine.symptom Receptor Transcription factor |
| Zdroj: | Genes and Cardiovascular Function ISBN: 9781441972064 |
| DOI: | 10.1007/978-1-4419-7207-1_14 |
| Popis: | Peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors, belong to the nuclear hormone receptor superfamily regulating expression of genes involved in different aspects of lipid metabolism and inflammation, and all three isoforms of PPAR (α, β/δ, and γ) detected so far modulate cardiac energy production. The activation of PPAR-α by its natural ligands, long-chain fatty acids (FAs) and eicosanoids, promotes mitochondrial FA oxidation as the primary ATP-generating pathway in the normal adult myocardium. Moreover, under physiological and pathological conditions associated with acute or chronic oxygen deprivation, PPAR-α modulates the expression of genes that determine myocardial substrate selection (FA vs. glucose) aimed at the maintenance of energy production to preserve basic cardiac function. However, whether PPAR activation plays a beneficial or detrimental role in myocardial response to ischemia/reperfusion (I/R) is still a matter of debate. Although PPAR-α and PPAR-γ agonists, hypolipidemic and antidiabetic drugs, have been reported to protect the heart against I/R, the role of PPARs in cardioprotection, in particular in pathological models, is not completely elucidated. This chapter 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 decreased susceptibility to ischemia in the experimental model of streptozotocin-induced diabetes, with particular regard to the role of PPAR gene expression and its modulation by concomitant pathology, such as hypercholesterolemia. Finally, the involvement of PPAR in the mechanisms of pleiotropic lipid-independent cardioprotective effects of some hypolipidemic drugs in both normal and diseased heart is also discussed. |
| Databáze: | OpenAIRE |
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