Abstract
Peroxisome proliferator activated receptor‐alpha (PPARa) is a lipogenic transcription factor known to exert pleiotropic effects in the cardiovascular system by mechanisms that are incompletely understood. We examined the effect of the PPARα agonist fenofibrate (FENO; 150 mg/kg/d for 4 weeks) on mitochondrial production of reactive oxygen species (ROS), lipoxidative stress, and the fatty acid composition of myocardial phospholipids in 14 month old male SHHF rats with severe hypertension and left ventricular (LV) hypertrophy. FENO had no significant effect on LV function or morphology, but significantly reduced mitochondrial ROS production and mitochondrial content of 4‐hydroxynonenal (HNE)‐protein adducts compared to untreated animals. Interestingly, FENO also induced a 50% decrease in relative proportion of arachidonic acid (20:4n6) and a 60% increase in DHA (22:6n3) in myocardial phospholipids, indicating potent alterations in the metabolism of polyunsaturated fatty acids favoring synthesis of anti‐ vs. pro‐inflammatory eicosanoids. The precise mechanisms and long‐term consequences of these novel phenomena are currently being examined in our laboratories. These studies suggest that FENO may elicit cardioprotective effects in the hypertrophied heart by reducing generation of ROS and altering polyunsaturated fatty acid metabolism. Supported by a grant from the American Heart Association.
Published Version
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