title: Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARgamma mRNA is present in cardiac myocytes; however, whether PPARgamma affects cardiac hypertrophy remains unknown.
  
  
  RESULTS
  We investigated the effects of PPARgamma 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 PPARgamma activators troglitazone and 15-deoxy-Delta(12-14)-prostaglandin J(2) (15d-PGJ(2)) (10 micromol/L) inhibited this effect (troglitazone, -72%, P<0.0005; 15d-PGJ(2), -88%, P<0.0002). Total cell protein was increased by mechanical strain (control, 164.3 microgram/dish; strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d-PGJ(2) (troglitazone, -61%, P<0.005; 15d-PGJ(2), -72%, P<0.001). [(3)H]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-PGJ(2) (troglitazone, -52% at 10 micromol/L, P<0.01; 15d-PGJ(2), -70% at 10 micromol/L, P<0.005). An increase in [(3)H]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ(2). Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPARgamma activators inhibited this induction. Furthermore, PPARgamma activators inhibited mechanically induced activation of nuclear factor (NF)-kappaB. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, inhibited strain-induced [(3)H]leucine uptake (-50% at 100 micromol/L, P<0.05).
  
  
  CONCLUSIONS
  These results demonstrate that PPARgamma activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPARgamma activators may regulate cardiomyocyte hypertrophy at least partially through the NF-kappaB pathway.
authors.affiliation: Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Tochigi, Japan. kyamamoto@jichi.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: R
authors.initials: R
authors.lastname: Ohki
authors.forename: R T
authors.initials: RT
authors.lastname: Lee
authors.forename: U
authors.initials: U
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Shimada
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D007930:Leucine / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D010656:Phenylephrine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013314:Stress, Mechanical; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D016328:NF-kappa B; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D010656:Phenylephrine; D007930:Leucine; D000077288:Troglitazone; D015230:Prostaglandin D2