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, and Nadia Rosenthal
European Molecular Biology Laboratory (M.P.S., J.C., E.L.-P., E. Slonimsky, E. Salimova, N.R.), Mouse Biology Unit Monterotondo (Rome), Italy; Beth Israel Deaconess Medical Center, Cardiovascular Division (L.T.), Boston, Mass; Mouse Clinical Institute (L.M.), Illkirch Cedex, France; VisualSonics Inc (C.T.), Toronto, Ontario, Canada; Tulane University Health Sciences Center, Section of Cardiology (P.D., Y.-H.S.), New Orleans, La; Franz Volhart Clinic at MDC (M.B., C.F.), Charite’ Campus Buch, University Medicine Berlin, Germany; Harefield Heart Science Centre (K.S.), Imperial College London, UK; and the University of Cambridge (J.C.), Addenbrookes Hospital, Cambridge, UK.
Circ. Res. published online May 24, 2007;

• > 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.
  
  NOTE: Echocardiographic analysis of injured hearts in eight 13 week-old males from wild-type and transgenic lines were analyzed by echocardiography 1 month after CTX injection in the left ventricle wall or after 1 month and 2 months after LCA ligation. Cardiac anatomy and function were measured with a Vevo 660 (VisualSonics) Ultrasound, and by the use of a 603 RMV (real-time-micro-visualization) scanhead (Visualsonics). The analysis was very sensitive due to the high-resolution images that the VisualSonics Ultrasound can acquire.