title: Enhancing repair of the mammalian heart.
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.
authors.affiliation: European Molecular Biology Laboratory, Mouse Biology Unit Monterotondo, Rome, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Santini
authors.forename: Lana
authors.initials: L
authors.lastname: Tsao
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
authors.forename: Catherine
authors.initials: C
authors.lastname: Theodoropoulos
authors.forename: Janice
authors.initials: J
authors.lastname: Carter
authors.forename: Enrique
authors.initials: E
authors.lastname: Lara-Pezzi
authors.forename: Esfir
authors.initials: E
authors.lastname: Slonimsky
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Salimova
authors.forename: Patrice
authors.initials: P
authors.lastname: Delafontaine
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Song
authors.forename: Martin
authors.initials: M
authors.lastname: Bergmann
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
authors.forename: Ken
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000503:physiopathology / Q000517:prevention & control; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D007249:Inflammation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D020127:Recovery of Function; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I