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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88 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1732 - 1740
Number of pages9
JournalCirculation Research
Volume100
Issue number12
Publication statusPublished - 2007
Externally publishedYes

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