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-Δ^12-14-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 troglitazone and 15d-PGJ₂ (troglitazone, −52% at 10 μmol/L, P<0.01; 15d-PGJ₂, −70% at 10 μmol/L, P<0.005). An increase in [³H]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ₂. Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPARγ activators inhibited this induction. Furthermore, PPARγ activators inhibited mechanically induced activation of nuclear factor (NF)-κB. Pyrrolidine dithiocarbamate, an inhibitor of NF-κB activation, inhibited strain-induced [³H]leucine uptake (−50% at 100 μmol/L, P<0.05).

Conclusions These results demonstrate that PPARγ activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPARγ activators may regulate cardiomyocyte hypertrophy at least partially through the NF-κB pathway.