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dc.contributor.authorMatsui, Takashi
dc.contributor.authorLi, Ling
dc.contributor.authorWu, Justina C.
dc.contributor.authorCook, Stuart
dc.contributor.authorNagoshi, Tomohisa
dc.contributor.authorPicard, Michael Howard
dc.contributor.authorLiao, Ronglih
dc.contributor.authorRosenzweig, Anthony
dc.date.accessioned2016-10-19T19:55:25Z
dc.date.issued2002
dc.identifier.citationMatsui, 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.en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29048920
dc.description.abstractThe 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.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Biochemistry & Molecular Biology (ASBMB)en_US
dc.relation.isversionofdoi:10.1074/jbc.M200347200en_US
dash.licenseLAA
dc.titlePhenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Hearten_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Biological Chemistryen_US
dash.depositing.authorPicard, Michael Howard
dc.date.available2016-10-19T19:55:25Z
dc.identifier.doi10.1074/jbc.M200347200*
dash.contributor.affiliatedWu, Justina
dash.contributor.affiliatedLiao, Ronglih
dash.contributor.affiliatedRosenzweig, Anthony
dash.contributor.affiliatedPicard, Michael


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