This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 100/12/1732    most recent CIRCRESAHA.107.148791v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santini, M. P. Articles by Rosenthal, N. Search for Related Content PubMed PubMed Citation Articles by Santini, M. P. Articles by Rosenthal, N. Related Collections Remodeling Cell signalling/signal transduction Growth factors/cytokines Heart failure - basic studies

(Circulation Research. 2007;100:1732.)
© 2007 American Heart Association, Inc.

Integrative Physiology

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 Rosenthal

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.

Correspondence to Nadia Rosenthal, Mouse Biology Unit Monterotondo, Rome, Italy. 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]