Controlling cardiomyocyte length: the role of renin and PPAR-{gamma}.
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.
Hinrichs
Söhnke
S
Physiologisches Institut, Justus-Liebig Universität Giessen, Aulweg 149, 35392 Gießen, Germany.
Heger
Jacqueline
J
Schreckenberg
Rolf
R
Wenzel
Sibylle
S
Euler
Gerhild
G
Arens
Christoph
C
Bader
Michael
M
Rosenkranz
Stephan
S
Caglayan
Evren
E
Schlüter
Klaus-Dieter
KD
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
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