title: Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo.
abstract: 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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest that the PPARgamma-dependent pathway is critically involved in the inhibition of cardiac hypertrophy.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Asakawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Uozumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Saito
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Masuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006579:Heterozygote; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077288:Troglitazone
chemical_list: D000199:Actins; D002839:Chromans; D007004:Hypoglycemic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D000077288:Troglitazone; D000077205:Pioglitazone