Published online before print May 24, 2007, doi: 10.1161/CIRCRESAHA.107.148791
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 17, 2007
Revised on April 15, 2007
Accepted on May 10, 2007
Enhancing Repair of the Mammalian Heart
Maria Paola Santini ;
From the 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.
* To whom correspondence should be addressed. E-mail: rosenthal{at}embl.it.
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.
Key words: cardiac muscle • insulin-like growth factor-1 • regeneration • wound healing
This article has been cited by other articles:
 |
|
 |
|
  D. P. Del Re and J. Sadoshima Optimizing Cell-Based Therapy for Cardiac Regeneration Circulation, September 8, 2009; 120(10): 831 - 834. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Korf-Klingebiel, T. Kempf, T. Sauer, E. Brinkmann, P. Fischer, G. P. Meyer, A. Ganser, H. Drexler, and K. C. Wollert Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction Eur. Heart J., December 1, 2008; 29(23): 2851 - 2858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Semenova, H. Koegel, S. Hasse, J. E. Klatte, E. Slonimsky, D. Bilbao, R. Paus, S. Werner, and N. Rosenthal Overexpression of mIGF-1 in Keratinocytes Improves Wound Healing and Accelerates Hair Follicle Formation and Cycling in Mice Am. J. Pathol., November 1, 2008; 173(5): 1295 - 1310. [Abstract] [Full Text] [PDF]
|
|