Peroxisome proliferator-activated receptor (PPAR)α is highly expressed in the heart. PPARα may play a role in cardiac hypertrophy, but effects on cardiac function, inflammation, and fibrosis are unknown. We tested the hypothesis that the PPARα activator fenofibrate prevents myocardial inflammation and fibrosis in angiotensin (Ang) II-infused rats.

Sprague Dawley rats received Ang II (120 ng/kg/min subcutaneously), fenofibrate (100 mg/kg/d p.o.), or Ang II + fenofibrate. After 7 d, systolic blood pressure (mmHg) was elevated (P < 0.01) in Ang II-infused rats (173 ± 4) vs. controls (115 ± 2) and reduced by fenofibrate (137 ± 5). Electrophoretic mobility shift assay demonstrated that Ang II upregulated cardiac nuclear factor kappa B activity by 50%. Ang II significantly increased cardiac expression of vascular-cell adhesion molecule-1, platelet endothelial cell adhesion molecule, and intercellular adhesion molecule-1. Increases in expression of these inflammatory mediators were normalized by fenofibrate. Ang II-induced expression of transforming growth factor-β1, collagen deposition, and macrophage infiltration were partially prevented by fenofibrate.

The PPARα activator fenofibrate prevented development of hypertension, and improved myocardial inflammation and collagen deposition in Ang II-infused rats. The hypolipidemic drug fenofibrate may be useful in prevention and treatment of myocardial disease associated with hypertension and hyperlipidemia.