Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

Journal Article · Thu Mar 10 04:00:00 EST 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2004.10.022· OSTI ID:20717552

Busk, Peter K ^[1]; Hinrichsen, Rebecca ^[2]; Bartkova, Jirina ^[3]; Hansen, Ane H ^[2]; Christoffersen, Tue E.H. ^[2]; Bartek, Jiri ^[3]; Haunso, Stig ^[2]

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1. Laboratory for Molecular Cardiology and The Heart Centre H:S, Rigshospitalet. 20, Juliane Mariesvej, DK-2100 Copenhagen O (Denmark) and Department of Virology and Molecular Toxicology, Novo Nordisk Park, 2760 Malov (Denmark)
2. Laboratory for Molecular Cardiology and The Heart Centre H:S, Rigshospitalet. 20, Juliane Mariesvej, DK-2100 Copenhagen O (Denmark)
3. Department of Cell Cycle and Cancer, Danish Cancer Society, 49, Strandboulevarden, DK-2100 Copenhagen O (Denmark)

The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21{sup Waf1/Cip1} and p27{sup Kip1}. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic under such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27{sup Kip1}. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2.

• OSTI ID: 20717552
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 304; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOTENSIN
CELL CYCLE
CELL DIVISION
CELL PROLIFERATION
HEART
HYPERTROPHY
INHIBITION
MITOGENS
MORPHOLOGY
PHOSPHORYLATION
SYNTHESIS