Published Online
on February 11, 2002

A more recent version of this article appeared on March 12, 2002

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Submitted on September 26, 2001
Revised on December 13, 2001
Accepted on January 3, 2002

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

Masayuki Asakawa MD, Hiroyuki Takano MD, PhD, Toshio Nagai MD, PhD, Hiroki Uozumi MD, PhD, Hiroshi Hasegawa MD, PhD, Naoto Kubota MD, PhD, Toshihiro Saito MD, PhD, Yoshiaki Masuda MD, PhD, Takashi Kadowaki MD, PhD, and Issei Komuro MD, PhD^*

From the Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan (M.A., H.T., T.N., H.H., T.S., Y.M., I.K.); the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (H.U.); and the Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (N.K., T.K.).

^* To whom correspondence should be addressed. E-mail: komuro-tky{at}umin.ac.jp.

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 PPAR, regulate growth of vascular cells. In the present study, we examined the role of PPAR 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 PPAR ligands such as troglitazone, pioglitazone, and rosiglitazone inhibited Ang II--induced upregulation of skeletal -actin and atrial natriuretic peptide genes and an increase in cell surface area. Treatment of mice with a PPAR 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 PPAR-deficient mice. In contrast, pressure overload--induced increases in the heart weight--to--body weight ratio and wall thickness were more prominent in heterozygous PPAR-deficient mice than in wild-type mice.

Conclusions—These results suggest that the PPAR-dependent pathway is critically involved in the inhibition of cardiac hypertrophy.

Key words: angiotensin • hypertrophy • myocytes • pressure

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