Granulocyte colony-stimulating factor treatment plus dipeptidylpeptidase-IV inhibition augments myocardial regeneration in mice expressing cyclin D2 in adult cardiomyocytes

Marc Michael Zaruba, Wuqiang Zhu, Mark Soonpaa, Sean Reuter, Wolfgang Michael Franz, Loren Field

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Aims: Although pharmacological interventions that mobilize stem cells and enhance their homing to damaged tissue can limit adverse post-myocardial infarction (MI) remodelling, cardiomyocyte renewal with this approach is limited. While experimental cell cycle induction can promote cardiomyocyte renewal following MI, this process must compete with the more rapid processes of scar formation and adverse remodelling. The current study tested the hypothesis that the combination of enhanced stem cell mobilization/homing and cardiomyocyte cell cycle induction would result in increased myocardial renewal in injured hearts. Methods and results: Myocardial infarction was induced by coronary artery ligation in adult MHC-cycD2 transgenic mice (which exhibit constitutive cardiomyocyte cell cycle activity) and their non-transgenic littermates. Mice were then treated with saline or with granulocyte colony-stimulating factor (G-CSF) plus the dipeptidylpeptidase-IV (DPP-IV) inhibitor Diprotin A (DipA) for 7 days. Infarct thickness and cardiomyocyte number/infarct/section were significantly improved in MHC-cycD2 mice with G-CSF plus DipA treatment when compared with MHC-cycD2 transgene expression or G-CSF plus DipA treatment alone. Echocardiographic analyses revealed that stem cell mobilization/homing and cardiomyocyte cell cycle activation had an additive effect on functional recovery. Conclusion: These data strongly suggest that G-CSF plus DPP-IV inhibition, combined with cardiomyocyte cell cycle activation, leads to enhanced myocardial regeneration following MI. The data are also consistent with the notion that altering adverse post-injury remodelling renders the myocardium more permissive for cardiomyocyte repopulation. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalEuropean Heart Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Cyclin D2
Granulocyte Colony-Stimulating Factor
Cardiac Myocytes
Regeneration
diprotin A
Cell Cycle
Myocardial Infarction
Hematopoietic Stem Cell Mobilization
Therapeutics
Transgenes
Transgenic Mice
Cicatrix
Ligation
Coronary Vessels
Myocardium
Stem Cells
Pharmacology

Keywords

  • Cardiomyocyte proliferation
  • DPP-IV/CD26 inhibition
  • Stem-cell mobilization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Granulocyte colony-stimulating factor treatment plus dipeptidylpeptidase-IV inhibition augments myocardial regeneration in mice expressing cyclin D2 in adult cardiomyocytes. / Zaruba, Marc Michael; Zhu, Wuqiang; Soonpaa, Mark; Reuter, Sean; Franz, Wolfgang Michael; Field, Loren.

In: European Heart Journal, Vol. 33, No. 1, 01.2012, p. 129-137.

Research output: Contribution to journalArticle

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