| First Author | Hinrichs S | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 89 |
| Issue | 2 | Pages | 344-52 |
| PubMed ID | 20884641 | Mgi Jnum | J:186891 |
| Mgi Id | MGI:5433467 | Doi | 10.1093/cvr/cvq313 |
| Citation | Hinrichs S, et al. (2011) Controlling cardiomyocyte length: the role of renin and PPAR-{gamma}. Cardiovasc Res 89(2):344-52 |
| abstractText | AIMS: Renin and peroxisome proliferator-activated receptor (PPAR-gamma) interact directly with cardiomyocytes and influence protein synthesis. We investigated their effects and interaction on the size of cardiomyocytes. METHODS AND RESULTS: Effects of renin and PPAR-gamma activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice with a cardiomyocyte-restricted knockout of PPAR-gamma, 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-gamma reduced cell length. Feeding wild-type mice with pioglitazone, a PPAR-gamma agonist, reduced cell length. Cardiomyocytes isolated from PPAR-gamma 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. CONCLUSION: 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-gamma. This type of cell size modification differs from that of any other known pro-hypertrophic agonists. |
