Peroxisome proliferator-activated receptor γ plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-03, Vol.105 (10), p.1240-1246
• Main Authors: ASAKAWA, Masayuki, TAKANO, Hiroyuki, NAGAI, Toshio, UOZUMI, Hiroki, HASEGAWA, Hiroshi, KUBOTA, Naoto, SAITO, Toshihiro, MASUDA, Yoshiaki, KADOWAKI, Takashi, KOMURO, Issei
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Angiotensin II - pharmacology; Animals; Atrial Natriuretic Factor - genetics; Atrial Natriuretic Factor - metabolism; Biological and medical sciences; Body Weight - drug effects; Cardiology. Vascular system; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomegaly - prevention & control; Cell Size - drug effects; Cells, Cultured; Chromans - pharmacology; Disease Models, Animal; Gene Expression - drug effects; Heart; Heart - drug effects; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heterozygote; Hypoglycemic Agents - pharmacology; Ligands; Medical sciences; Mice; Mice, Knockout; Myocardium - cytology; Myocardium - metabolism; Myocardium - pathology; Organ Size - drug effects; Pioglitazone; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear - deficiency; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Rosiglitazone; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - metabolism; Troglitazone
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc1002.105225

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 PPARgamma, regulate growth of vascular cells. In the present study, we examined the role of PPARgamma in angiotensin II (Ang II)-induced hypertrophy of neonatal rat cardiac myocytes and in pressure overload-induced cardiac hypertrophy of mice. Treatment of cultured cardiac myocytes with PPARgamma ligands such as troglitazone, pioglitazone, and rosiglitazone inhibited Ang II-induced upregulation of skeletal alpha-actin and atrial natriuretic peptide genes and an increase in cell surface area. Treatment of mice with a PPARgamma 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 PPARgamma-deficient mice. In contrast, pressure overload-induced increases in the heart weight-to-body weight ratio and wall thickness were more prominent in heterozygous PPARgamma-deficient mice than in wild-type mice. These results suggest that the PPARgamma-dependent pathway is critically involved in the inhibition of cardiac hypertrophy.