The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment

Ryo Suzuki, Tao Sheng Li, Akihito Mikamo, Masaya Takahashi, Mako Ohshima, Masayuki Kubo, Hiroshi Ito, Kimikazu Hamano

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15 Citations (Scopus)

Abstract

Objectives: Mitotic cardiomyocytes and cardiac stem cells have been identified recently in adult hearts, and both have been found to be increased in acute infarcted myocardium. Although these findings suggest potential self-repair of the heart after injury, obvious self-regeneration of the injured heart has never been observed clinically. We hypothesized that hemodynamic loading impairs myocardial repair. Methods: Myocardial infarction was induced in C57BL/6 mice by ligating the left anterior descending artery. After 60 minutes, either the infarcted heart was transplanted heterotopically into a healthy recipient C57BL/6 mouse to remove the ventricular hemodynamic loading (unloading group) or it was left as an infarcted heart under normal hemodynamic loading conditions in the same mouse (loading group). The infarcted hearts were dissected for histologic analysis after 3, 7, 14, and 28 days. Results: Histologic analysis showed that the wall thickness of the infarcted left ventricle was significantly greater and the area of infarction was significantly smaller in the unloading group than in the loading group. Immunostaining analysis revealed significantly more Ki-67-positive cells and significantly fewer apoptotic cells in the infarcted myocardium in the unloading group than in the loading group. There were also significantly more c-kit- and Sca-1-positive stem cells in the infarcted myocardium in the unloading group than in the loading group. Conclusion: Our findings suggest that hemodynamic unloading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment.

Original languageEnglish
Pages (from-to)1051-1058
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume133
Issue number4
DOIs
Publication statusPublished - Apr 1 2007

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ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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