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| Item Type: | Article |
|---|---|
| Title: | Enhancing repair of the mammalian heart |
| Creators Name: | Santini, M.P., Tsao, L., Monassier, L., Theodoropoulos, C., Carter, J., Lara-Pezzi, E., Slonimsky, E., Salimova, E., Delafontain, P., Song, Y.H., Bergmann, M., Freund, C., Suzuki, K. and Rosenthal, N. |
| Abstract: | The injured mammalian heart is particularly susceptible to tissue deterioration, scarring, and loss of contractile function in response to trauma or sustained disease. We tested the ability of a locally acting insulin-like growth factor-1 isoform (mIGF-1) to recover heart functionality, expressing the transgene in the mouse myocardium to exclude endocrine effects on other tissues. supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. The canonical signaling pathway involving Akt, mTOR, and p70S6 kinase was not induced in mIGF-1 hearts, which instead activated alternate PDK1 and SGK1 signaling intermediates. The robust response achieved with the mIGF-1 isoform provides a mechanistic basis for clinically feasible therapeutic strategies for improving the outcome of heart disease. |
| Keywords: | Cardiac Muscle, Insulin-Like Growth Factor-1, Regeneration, Wound Healing, Animals, Mice |
| Source: | Circulation Research |
| ISSN: | 0009-7330 |
| Publisher: | American Heart Association |
| Volume: | 100 |
| Number: | 12 |
| Page Range: | 1732-1740 |
| Date: | 22 June 2007 |
| Official Publication: | https://doi.org/10.1161/CIRCRESAHA.107.148791 |
| PubMed: | View item in PubMed |
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