Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction

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

Research output: Contribution to journalArticle

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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
Pages (from-to)18-25
Number of pages8
JournalCardiovascular Research
Volume78
Issue number1
DOIs
StatePublished - Apr 2008

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Cardiac Myocytes
Cell Cycle
Myocardial Infarction
Myocardium
Cyclin D2
Genetically Modified Animals
Coronary Occlusion
Wounds and Injuries
Ventricular Pressure
Giant Cells
Transgenic Mice
Regeneration
Heart Diseases
Coronary Vessels
Calcium

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction. / Hassink, Rutger J.; Pasumarthi, Kishore B.; Nakajima, Hidehiro; Rubart-von der Lohe, Michael; Soonpaa, Mark; De La Rivière, Aart Brutel; Doevendans, Pieter A.; Field, Loren.

In: Cardiovascular Research, Vol. 78, No. 1, 04.2008, p. 18-25.

Research output: Contribution to journalArticle

Hassink, Rutger J. ; Pasumarthi, Kishore B. ; Nakajima, Hidehiro ; Rubart-von der Lohe, Michael ; Soonpaa, Mark ; De La Rivière, Aart Brutel ; Doevendans, Pieter A. ; Field, Loren. / Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction. In: Cardiovascular Research. 2008 ; Vol. 78, No. 1. pp. 18-25.
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