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Enhancing repair of the mammalian heart.
- Source :
-
Circulation research [Circ Res] 2007 Jun 22; Vol. 100 (12), pp. 1732-40. Date of Electronic Publication: 2007 May 24. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Cell Proliferation
Cells, Cultured
Cicatrix physiopathology
Cicatrix prevention & control
DNA, Complementary genetics
Gene Expression Regulation
Inflammation
Insulin-Like Growth Factor I genetics
Mice
Mice, Transgenic
Myocardial Contraction physiology
Myocardial Infarction physiopathology
Myocytes, Cardiac cytology
Protein Isoforms genetics
Protein Isoforms physiology
Recovery of Function
Signal Transduction physiology
Wound Healing genetics
Insulin-Like Growth Factor I physiology
Myocardial Infarction complications
Myocytes, Cardiac physiology
Wound Healing physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 100
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 17525368
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.107.148791