Journal
CIRCULATION RESEARCH
Volume 100, Issue 12, Pages 1732-1740Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.107.148791
Keywords
cardiac muscle; insulin-like growth factor-1; regeneration; wound healing
Funding
- Medical Research Council [G0600872] Funding Source: researchfish
- MRC [G0600872] Funding Source: UKRI
- Medical Research Council [G0600872] Funding Source: Medline
- NHLBI NIH HHS [R01 HL080682, R01 HL080682-05] Funding Source: Medline
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available