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The peroxisome proliferators-activated receptor-alpha (PPARalpha), a transcription factor that modulates fatty acid metabolism, regulates substrate preference in the heart. Although in acute ischemia there is a switch in substrate preference from fatty acids to glucose, metabolic gene expression in repetitive ischemia is not well described. In a mouse model of ischemic cardiomyopathy induced by repetitive ischemia/reperfusion (I/R), we postulated that downregulation of PPARalpha is regulated by reactive oxygen species and is necessary for maintaining contractile function in the heart.

circulation

Downregulation of Peroxisome Proliferator–Activated Receptor-α Gene Expression in a Mouse Model of Ischemic Cardiomyopathy Is Dependent on Reactive Oxygen Species and Prevents Lipotoxicity