Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium.
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 cardiomyocyte 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.
Chaudhry
Hina W
HW
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. hwc7@columbia.edu
Dashoush
Nurin H
NH
Tang
Haiying
H
Zhang
Ling
L
Wang
Xiangyuan
X
Wu
Ed X
EX
Wolgemuth
Debra J
DJ
D000818:Animals; D019925:Cyclin A / Q000502:physiology*; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology
D019925:Cyclin A