Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction

Rutger J. Hassink, Kishore B. Pasumarthi, Hidehiro Nakajima, Michael Rubart, Mark H. Soonpaa, Aart Brutel De La Rivière, Pieter A. Doevendans, Loren J. Field

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Aims: Cardiomyocyte loss is a major contributor to the decreased cardiac function observed in diseased hearts. Previous studies have shown that cardiomyocyte-restricted cyclin D2 expression resulted in sustained cell cycle activity following myocardial injury in transgenic (MHC-cycD2) mice. Here, we investigated the effects of this cell cycle activation on cardiac function following myocardial infarction (MI). Methods and results: MI was induced in transgenic and non-transgenic mice by left coronary artery occlusion. At 7, 60, and 180 days after MI, left ventricular pressure-volume measurements were recorded and histological analysis was performed. MI had a similar adverse effect on cardiac function in transgenic and non-transgenic mice at 7 days post-injury. No improvement in cardiac function was observed in non-transgenic mice at 60 and 180 days post-MI. In contrast, the transgenic animals exhibited a progressive and marked increase in cardiac function at subsequent time points. Improved cardiac function in the transgenic mice at 60 and 180 days post-MI correlated positively with the presence of newly formed myocardial tissue which was not apparent at 7 days post-MI. Intracellular calcium transient imaging indicated that cardiomyocytes present in the newly formed myocardium participated in a functional syncytium with the remote myocardium. Conclusion: These findings indicate that cardiomyocyte cell cycle activation leads to improvement of cardiac function and morphology following MI and may represent an important clinical strategy to promote myocardial regeneration.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalCardiovascular research
Volume78
Issue number1
DOIs
StatePublished - Apr 2008

Keywords

  • Cardiac function
  • Cardiac regeneration
  • Cardiomyocyte cell cycle activation
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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