Deletion of peroxisome proliferator-activated receptor-α induces an alteration of cardiac functions

The peroxisome proliferator-activated receptor-alpha (PPAR alpha) plays a major role in the control of cardiac energy metabolism. The role of PPAR alpha on cardiac functions was evaluated by using PPAR alpha knockout (PPAR alpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPAR alpha did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPAR alpha -/- mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPAR alpha (-/-) mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPAR alpha -/- mice was lower compared with wild-type (PPAR alpha -/-) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and beta-adrenergic agonist-induced developed forces were significantly reduced in PPAR alpha-null mice. In addition, Western blot analysis shows that the protein expression of beta 1-adrenergic receptor is reduced in hearts from PPAR alpha -/- mice. Histological analysis showed that hearts from PPAR alpha -/- but not PPAR alpha -/- mice displayed myocardial fibrosis. These results suggest that PPAR alpha- null mice have an alteration of cardiac contractile performance under basal and under stimulation of beta 1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPAR alpha in maintaining cardiac functions.