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Different regulation of p27 and Akt during cardiomyocyte proliferation and hypertrophy

Rebecca Hinrichsen1, Stig Haunsø, Peter K Busk

  • 1Cell Biology, Biosystems Department, Risø National Laboratory, DK-4000 Roskilde, Denmark. r.hinrichsen@jubii.dk

Growth Factors (Chur, Switzerland)
|September 14, 2007
PubMed

Insights

Neonatal cardiomyocytes exhibit distinct growth patterns. Angiotensin II promotes hypertrophy, while PDGF stimulates proliferation by modulating cell cycle regulators like p27 and Akt.

Area of Science:

  • Cardiology
  • Cell Biology
  • Molecular Biology

Background:

  • Postnatal cardiomyocytes primarily grow via hypertrophy.
  • Neonatal cardiomyocytes retain some proliferative capacity, responding to specific stimuli.
  • Understanding the molecular mechanisms differentiating hypertrophic and proliferative growth is crucial.

Purpose of the Study:

  • To investigate the molecular distinctions between hypertrophic and proliferative growth in neonatal cardiomyocytes.
  • To compare the effects of Angiotensin II and Platelet-Derived Growth Factor (PDGF) on cardiomyocyte growth.

Main Methods:

  • Primary neonatal cardiomyocyte cultures.
  • Stimulation with Angiotensin II and PDGF.
  • Immunohistochemistry to assess pRb phosphorylation (G1 cell cycle phase).
  • Western blotting to analyze Akt, GSK-3beta, and p27 expression.

Main Results:

  • Angiotensin II predominantly induced cardiomyocyte hypertrophy.
  • PDGF significantly stimulated cardiomyocyte proliferation, with minimal hypertrophic effect.
  • Both stimuli activated the G1 phase of the cell cycle.
  • PDGF-induced proliferation correlated with Akt activation, GSK-3beta inactivation, and p27 downregulation.
  • Angiotensin II showed limited effects on Akt, GSK-3beta, and p27.

Conclusions:

  • Both hypertrophic and proliferative cardiomyocyte growth are initiated by G1 cell cycle molecules.
  • Hypertrophic growth is associated with high p27 levels.
  • Proliferative growth involves p27 and GSK-3beta downregulation, and Akt upregulation.

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