Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions.
The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major role in the control of cardiac energy metabolism. The role of PPARalpha on cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARalpha 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 PPARalpha -/- mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARalpha -/- mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARalpha -/- mice was lower compared with wild-type (PPARalpha +/+) 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 PPARalpha-null mice. In addition, Western blot analysis shows that the protein expression of beta1-adrenergic receptor is reduced in hearts from PPARalpha -/- mice. Histological analysis showed that hearts from PPARalpha -/- but not PPARalpha +/+ mice displayed myocardial fibrosis. These results suggest that PPARalpha-null mice have an alteration of cardiac contractile performance under basal and under stimulation of beta1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARalpha in maintaining cardiac functions.
Loichot
Cécile
C
Laboratorie de Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, UMR-Centre National de la Recherche Scientifique (CNRS) 7034, Faculté de Pharmacie, Université Louis Pasteur (ULP), Illkirch, France.
Jesel
Laurence
L
Tesse
Angela
A
Tabernero
Antonia
A
Schoonjans
Kristina
K
Roul
Gérard
G
Carpusca
Irina
I
Auwerx
Johan
J
Andriantsitohaina
Ramaroson
R
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D017353:Gene Deletion; D006352:Heart Ventricles / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000502:physiology*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000502:physiology*
D047493:PPAR alpha; D018342:Receptors, Adrenergic, beta-1