Circulation Research. 2005;96:110-118
Published online before print December 2, 2004, doi: 10.1161/01.RES.0000152326.91223.4F
Published online before print December 2, 2004, doi: 10.1161/01.RES.0000152326.91223.4F
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© 2005 American Heart Association, Inc.
Integrative Physiology |
Targeted Expression of Cyclin D2 Results in Cardiomyocyte DNA Synthesis and Infarct Regression in Transgenic Mice
From the Wells Center for Pediatric Research and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Ind. Present address of K.B.S. Pasumarthi is Dalhousie University, Halifax, Canada.
Correspondence to Loren J. Field, Herman B Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, 1044 West Walnut St, R4-W376, Indianapolis, IN 46202-5225. E-mail ljfield{at}iupui.edu
Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating partners, the D-type cyclins. In this study, we examined the ability of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic mice expressing cyclin D1, D2, or D3 under the regulation of the 
cardiac myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis under baseline conditions. Cardiac injury in mice expressing cyclin D1 or D3 resulted in cytoplasmic cyclin D accumulation, with a concomitant reduction in the level of cardiomyocyte DNA synthesis. In contrast, cardiac injury in mice expressing cyclin D2 did not alter subcellular cyclin localization. Consequently, cardiomyocyte cell cycle activity persisted in injured hearts expressing cyclin D2, ultimately resulting in infarct regression. These data suggested that modulation of D-type cyclins could be exploited to promote regenerative growth in injured hearts.
Key Words: cardiomyocyte proliferation • DNA synthesis • heart regeneration
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