Expression of mutant p193 and p53 permits cardiomyocyte cell cycle reentry after myocardial infarction in transgenic mice

Hidehiro Nakajima, Hisako O. Nakajima, Shih Chong Tsai, Loren Field

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell-derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell cycle activity in normal and infarcted hearts were examined. Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants in the heart were generated. Transgene expression had no effect on cardiomyocyte cell cycle activity in uninjured adult hearts. In contrast expression of either transgene resulted in a marked induction of cardiomyocyte cell cycle activity at the infarct border zone at 4 weeks after permanent coronary artery occlusion. Expression of the p193 dominant-interfering mutant was also associated with an induction of cardiomyocyte DNA synthesis in the interventricular septa of infarcted hearts. A concomitant and marked reduction in hypertrophic cardiomyocyte growth was observed in the septa of hearts expressing the p193 dominant-interfering transgene, suggesting that cell cycle activation might partially counteract the adverse ventricular remodeling that occurs after infarction. Collectively these data suggest that antagonization of p193 and p53 activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle reentry in the injured adult heart.

Original languageEnglish
Pages (from-to)1606-1614
Number of pages9
JournalCirculation Research
Volume94
Issue number12
DOIs
StatePublished - Jun 25 2004

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Cardiac Myocytes
Transgenic Mice
Cell Cycle
Myocardial Infarction
Heart Septum
Transgenes
Ventricular Remodeling
Coronary Occlusion
Oncogene Proteins
Embryonic Stem Cells
Infarction
Coronary Vessels
DNA
Growth

Keywords

  • Apoptosis
  • Cardiomyocyte proliferation
  • DNA synthesis
  • Heart regeneration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Expression of mutant p193 and p53 permits cardiomyocyte cell cycle reentry after myocardial infarction in transgenic mice. / Nakajima, Hidehiro; Nakajima, Hisako O.; Tsai, Shih Chong; Field, Loren.

In: Circulation Research, Vol. 94, No. 12, 25.06.2004, p. 1606-1614.

Research output: Contribution to journalArticle

Nakajima, Hidehiro ; Nakajima, Hisako O. ; Tsai, Shih Chong ; Field, Loren. / Expression of mutant p193 and p53 permits cardiomyocyte cell cycle reentry after myocardial infarction in transgenic mice. In: Circulation Research. 2004 ; Vol. 94, No. 12. pp. 1606-1614.
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