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Cardiomyocyte cell cycle control and growth estimation in vivo- an analysis based on cardiomyocyte nuclei.

Walsh, Stuart LU ; Pontén, Annica LU ; Fleischmann, Bernd K and Jovinge, Stefan LU (2010) In Cardiovascular Research 86(3). p.365-373
Abstract
AIMS: Adult mammalian cardiomyocytes are traditionally viewed as being permanently withdrawn from the cell cycle. While some groups have reported none, others have reported extensive mitosis in adult myocardium under steady state conditions. Recently, a highly specific assay of (14)C dating in humans has suggested a continuous generation of cardiomyocytes in the adult, albeit at a very low rate. Mice represent the most commonly used animal model for these studies, but their short life-span makes them unsuitable for (14)C studies. Herein we investigate the cellular growth pattern for murine cardiomyocyte growth under steady-state conditions, addressed with new analytical and technical strategies, and we furthermore relate this to gene... (More)
AIMS: Adult mammalian cardiomyocytes are traditionally viewed as being permanently withdrawn from the cell cycle. While some groups have reported none, others have reported extensive mitosis in adult myocardium under steady state conditions. Recently, a highly specific assay of (14)C dating in humans has suggested a continuous generation of cardiomyocytes in the adult, albeit at a very low rate. Mice represent the most commonly used animal model for these studies, but their short life-span makes them unsuitable for (14)C studies. Herein we investigate the cellular growth pattern for murine cardiomyocyte growth under steady-state conditions, addressed with new analytical and technical strategies, and we furthermore relate this to gene expression patterns. Methods and Results The observed levels of DNA synthesis in early life were associated with cardiomyocyte proliferation. Mitosis was prolonged into early life, longer than the most conservative previous estimates. DNA synthesis in neonatal life was attributable to bi-nucleation, therefore suggesting that cardiomyocytes withdraw from the cell cycle shortly after birth. No cell cycle activity was observed in adult cardiomyocytes and significant polyploidy was observed in cardiomyocyte nuclei. CONCLUSIONS: Gene analyses identified 32 genes whose expression was predicted to be particular to day 3-4 neonatal myocytes, compared to embryonic or adult cells. These cell cycle-associated genes are crucial to the understanding of the mechanisms of bi-nucleation and physiological cellular growth in the neonatal period. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cardiovascular Research
volume
86
issue
3
pages
365 - 373
publisher
Elsevier
external identifiers
  • wos:000277732000005
  • pmid:20071355
  • scopus:77952371023
ISSN
1755-3245
DOI
10.1093/cvr/cvq005
language
English
LU publication?
yes
id
89ee6f06-aa10-45d3-bbac-b34440a87b7a (old id 1541097)
alternative location
http://cardiovascres.oxfordjournals.org/content/86/3/365.full
date added to LUP
2010-02-02 13:34:22
date last changed
2018-07-15 04:19:26
@article{89ee6f06-aa10-45d3-bbac-b34440a87b7a,
  abstract     = {AIMS: Adult mammalian cardiomyocytes are traditionally viewed as being permanently withdrawn from the cell cycle. While some groups have reported none, others have reported extensive mitosis in adult myocardium under steady state conditions. Recently, a highly specific assay of (14)C dating in humans has suggested a continuous generation of cardiomyocytes in the adult, albeit at a very low rate. Mice represent the most commonly used animal model for these studies, but their short life-span makes them unsuitable for (14)C studies. Herein we investigate the cellular growth pattern for murine cardiomyocyte growth under steady-state conditions, addressed with new analytical and technical strategies, and we furthermore relate this to gene expression patterns. Methods and Results The observed levels of DNA synthesis in early life were associated with cardiomyocyte proliferation. Mitosis was prolonged into early life, longer than the most conservative previous estimates. DNA synthesis in neonatal life was attributable to bi-nucleation, therefore suggesting that cardiomyocytes withdraw from the cell cycle shortly after birth. No cell cycle activity was observed in adult cardiomyocytes and significant polyploidy was observed in cardiomyocyte nuclei. CONCLUSIONS: Gene analyses identified 32 genes whose expression was predicted to be particular to day 3-4 neonatal myocytes, compared to embryonic or adult cells. These cell cycle-associated genes are crucial to the understanding of the mechanisms of bi-nucleation and physiological cellular growth in the neonatal period.},
  author       = {Walsh, Stuart and Pontén, Annica and Fleischmann, Bernd K and Jovinge, Stefan},
  issn         = {1755-3245},
  language     = {eng},
  number       = {3},
  pages        = {365--373},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {Cardiomyocyte cell cycle control and growth estimation in vivo- an analysis based on cardiomyocyte nuclei.},
  url          = {http://dx.doi.org/10.1093/cvr/cvq005},
  volume       = {86},
  year         = {2010},
}