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Publication : Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium.

First Author  Chaudhry HW Year  2004
Journal  J Biol Chem Volume  279
Issue  34 Pages  35858-66
PubMed ID  15159393 Mgi Jnum  J:92551
Mgi Id  MGI:3053491 Doi  10.1074/jbc.M404975200
Citation  Chaudhry HW, et al. (2004) Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium. J Biol Chem 279(34):35858-66
abstractText  Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyoctye mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.
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