Peroxisome Proliferator-Activated Receptor γ Plays a Critical Role in Inhibition of Cardiac Hypertrophy In Vitro and In Vivo

Background— Peroxisome proliferator-activated receptors (PPARs) are transcription factors of the nuclear receptor superfamily. It has been reported that the thiazolidinediones, which are antidiabetic agents and high-affinity ligands for PPARγ, regulate growth of vascular cells. In the present study, we examined the role of PPARγ in angiotensin II (Ang II)-induced hypertrophy of neonatal rat cardiac myocytes and in pressure overload-induced cardiac hypertrophy of mice. Methods and Results— Treatment of cultured cardiac myocytes with PPARγ ligands such as troglitazone, pioglitazone, and rosiglitazone inhibited Ang II-induced upregulation of skeletal α-actin and atrial natriuretic peptide genes and an increase in cell surface area. Treatment of mice with a PPARγ ligand, pioglitazone, inhibited pressure overload-induced increases in the heart weight-to-body weight ratio, wall thickness, and myocyte diameter in wild-type mice and an increase in the heart weight-to-body weight ratio in heterozygous PPARγ-defici...