title: Controlling cardiomyocyte length: the role of renin and PPAR-{gamma}.
abstract: OBJECTIVE
  Renin and peroxisome proliferator-activated receptor (PPAR-γ) interact directly with cardiomyocytes and influence protein synthesis. We investigated their effects and interaction on the size of cardiomyocytes.
  
  
  RESULTS
  Effects of renin and PPAR-γ activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice with a cardiomyocyte-restricted knockout of PPAR-γ, and transgenic rats overexpressing renin, TGR(mRen2)27. The length and width of cardiomyocytes were analysed 24 h after administration of factors. Renin caused an unexpected effect on the length of cardiomyocytes that was inhibited by mannose-6-phosphate and monensin, but not by administration of glucose-6-phosphate. Endothelin-1 used as a classical pro-hypertrophic agonist increased cell width but not cell length. Renin caused an activation of p38 and p42/44 mitogen-activated protein (MAP) kinases. The latter activation was impaired by mannose-6-phosphate. Inhibition of p42/44 but not of p38 MAP kinase activation attenuated the effect of renin on cell length. In contrast, activation of PPAR-γ reduced cell length. Feeding wild-type mice with pioglitazone, a PPAR-γ agonist, reduced cell length. Cardiomyocytes isolated from PPAR-γ knockout mice were longer, and their length was not affected by pioglitazone. Cardiomyocytes isolated from TGR(mRen2)27 rats were longer than those of non-transgenic littermates. Cell length was reduced by feeding these mice with pioglitazone. Pioglitazone affected cell length independent of blood pressure.
  
  
  CONCLUSIONS
  The length of cardiomyocytes is controlled by the activation of cardiac-specific mannose-6-phosphate/insulin-like growth factor II receptors and activation of PPAR-γ. This type of cell size modification differs from that of any other known pro-hypertrophic agonists.
authors.affiliation: Physiologisches Institut, Justus-Liebig Universität Giessen, Aulweg 149, 35392 Gießen, Germany.
authors.forename: Söhnke
authors.initials: S
authors.lastname: Hinrichs
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Heger
authors.forename: Rolf
authors.initials: R
authors.lastname: Schreckenberg
authors.forename: Sibylle
authors.initials: S
authors.lastname: Wenzel
authors.forename: Gerhild
authors.initials: G
authors.lastname: Euler
authors.forename: Christoph
authors.initials: C
authors.lastname: Arens
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Evren
authors.initials: E
authors.lastname: Caglayan
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schlüter
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008360:Mannosephosphates / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D005419:Flavonoids; D007093:Imidazoles; D008360:Mannosephosphates; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017527:Receptor, IGF Type 2; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; C473112:Ren2 protein, mouse; D045162:Thiazolidinediones; C034304:cation-dependent mannose-6-phosphate receptor; C027693:mannose-6-phosphate; D002216:Captopril; D020928:Mitogen-Activated Protein Kinases; D012083:Renin; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077205:Pioglitazone