Peroxisome Proliferator-Activated Receptor γ Activators Inhibit Cardiac Hypertrophy in Cardiac Myocytes

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Abstract
Background Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARγ mRNA is present in cardiac myocytes; however, whether PPARγ affects cardiac hypertrophy remains unknown. Methods and Results We investigated the effects of PPARγ activators on cardiac hypertrophy in neonatal rat cardiac myocytes. Cyclic 4% biaxial mechanical strain caused enlargement of cardiac myocytes (1.3-fold versus control, P<0.0001), but the PPARγ activators troglitazone and 15-deoxy-Δ12-14-prostaglandin J2 (15d-PGJ2) (10 μmol/L) inhibited this effect (troglitazone, −72%, P<0.0005; 15d-PGJ2, −88%, P<0.0002). Total cell protein was increased by mechanical strain (control, 164.3 μg/dish; strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d-PGJ2 (troglitazone, −61%, P<0.005; 15d-PGJ2, −72%, P<0.001). [3H]Leucine uptake was also increased by mechanical strain (1.9-fold versus control, P<0.002), and this increase was inhibited by troglita...