Phenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Heart
Author
Matsui, Takashi
Li, Ling
Cook, Stuart
Nagoshi, Tomohisa
Published Version
https://doi.org/10.1074/jbc.M200347200Metadata
Show full item recordCitation
Matsui, Takashi, Ling Li, Justina C. Wu, Stuart A. Cook, Tomohisa Nagoshi, Michael H. Picard, Ronglih Liao, and Anthony Rosenzweig. 2002. Phenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Heart. Journal of Biological Chemistry 277, no. 25: 22896–22901. doi:10.1074/jbc.m200347200. http://dx.doi.org/10.1074/jbc.M200347200.Abstract
The serine-threonine kinase, Akt, inhibits cardiomyocyte apoptosis acutely both in vitro and in vivo. However, the effects of chronic Akt activation in the heart are unknown. To address this issue, we generated transgenic mice (TG ) with cardiac-specific expression of a constitutively active mutant of Akt (myr-Akt) driven by the myosin heavy chain- promoter. Three TG founders (9–19 weeks) died suddenly with massive cardiac dilatation. Two viable TG lines (TG564 and TG20) derived from independent founders demonstrated cardiac-specific transgene expression as well as activation of Akt and p70S6 kinase. TG564 (n 19) showed cardiac hypertrophy with a heart/body weight ratio 2.3-fold greater than littermates (n 17, p < 0.005). TG20 (n 18) had less marked cardiac hypertrophy with a heart/body weight ratio 1.6-fold greater than littermates (n 17, p < 0.005). Isolated TG564 myocytes were also hypertrophic with surface areas 1.7-fold greater than littermates (p < 0.000001). Echocardiograms in both lines demonstrated concentric hypertrophy and preserved systolic function. After ischemia-reperfusion, TG had a 50% reduction in infarct size versus TG (17 3% versus 34 4%, p < 0.001). Thus, chronic Akt activation is sufficient to cause a spectrum of phenotypes from moderate cardiac hypertrophy with preserved systolic function and cardioprotection to massive cardiac dilatation and sudden death.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:29048920
Collections
- HMS Scholarly Articles [17301]
Contact administrator regarding this item (to report mistakes or request changes)