Enhancing repair of the mammalian heart

Maria Paola Santini, Lana Tsao, Laurent Monassier, Catherine Theodoropoulos, Janice Carter, Enrique Lara-Pezzi, Esfir Slonimsky, Ekaterina Salimova, Patrice Delafontaine, Yao-Hua Song, Martin Bergmann, Christian Freund, Ken Suzuki, Nadia Alicia Rosenthal

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95 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1732 - 1740
Number of pages9
JournalCirculation Research
Issue number12
Publication statusPublished - 2007
Externally publishedYes

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