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Enhancing repair of the mammalian heart

Item Type:Article
Title:Enhancing repair of the mammalian heart
Creators Name:Santini, M.P. and Tsao, L. and Monassier, L. and Theodoropoulos, C. and Carter, J. and Lara-Pezzi, E. and Slonimsky, E. and Salimova, E. and Delafontain, P. and Song, Y.H. and Bergmann, M. and Freund, C. and 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
Publisher:American Heart Association
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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