Cardiomyocyte cell cycle activation ameliorates fibrosis in the atrium

Hidehiro Nakajima, Hisako O. Nakajima, Klaus Dembowsky, Kishore B.S. Pasumarthi, Loren J. Field

Research output: Contribution to journalArticle

21 Scopus citations


MHC-TGFcysser transgenic mice have elevated levels of active transforming growth factor (TGF)-β1 in the myocardium. Previous studies have shown that these animals develop atrial, but not ventricular, fibrosis. Here we show that atrial fibrosis was accompanied with cardiomyocyte apoptosis. Although similar levels of cardiomyocyte apoptosis were present in the right and left atria of MHC-TGFcysser hearts, the extent of fibrosis was more pronounced in the right atrium. Thus, additional factors influence the degree of atrial fibrosis in this model. Tritiated thymidine incorporation studies revealed cardiomyocyte cell cycle activity in left atrial cardiomyocytes, but not in right atrial cardiomyocytes. These observations suggested that cardiomyocyte cell cycle activation ameliorated the severity of atrial fibrosis. To directly test this hypothesis, MHC-TGFcysser mice were crossed with MHC-cycD2 mice (which have constitutive cardiomyocyte cell cycle activity in the right atrium). Mice inheriting both transgenes exhibited right atrial cardiomyocyte cell cycle activity and a concomitant reduction in the severity of right atrial fibrosis, despite the presence of a similar level of cardiomyocyte apoptosis as was observed in mice inheriting the MHC-TGFcysser transgene alone. These data support the notion that cardiomyocyte cell cycle induction can antagonize fibrosis in the myocardium.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalCirculation research
Issue number1
StatePublished - Jan 2006


  • Cardiac myocyte apoptosis
  • Cardiomyocyte proliferation
  • Heart regeneration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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