| First Author | Santini MP | Year | 2007 |
| Journal | Circ Res | Volume | 100 |
| Issue | 12 | Pages | 1732-40 |
| PubMed ID | 17525368 | Mgi Jnum | J:137808 |
| Mgi Id | MGI:3802902 | Doi | 10.1161/CIRCRESAHA.107.148791 |
| Citation | Santini MP, et al. (2007) Enhancing repair of the mammalian heart. Circ Res 100(12):1732-40 |
| abstractText | 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. |
