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

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