Chronic Treatment with Clenbuterol Modulates Endothelial Progenitor Cells and Circulating Factors in a Murine Model of Cardiomyopathy

  • James E. Rider
  • Sean P. Polster
  • Sangjin Lee
  • Nathan J. Charles
  • Neeta Adhikari
  • Ami Mariash
  • George Tadros
  • Jenna Stangland
  • Ryszard T. Smolenski
  • Cesare M Terracciano
  • Paul J.R. Barton
  • Emma J. Birks
  • Magdi H. Yacoub
  • Leslie W. Miller
  • Jennifer L. Hall
Article

Abstract

The purpose of this study was to determine the effects of chronic treatment with the beta 2 adrenergic receptor agonist clenbuterol on endothelial progenitor cells (EPC) in a well-characterized model of heart failure, the muscle LIM protein knockout (MLP−/−) mouse. MLP−/− mice were treated daily with clenbuterol (2 mg/kg) or saline subcutaneously for 6 weeks. Clenbuterol led to a 30% increase in CD31+ cells in the bone marrow of MLP−/− heart failure mice (p < 0.004). Clenbuterol did not improve ejection fraction. Clenbuterol treatment in MLP−/− mice was associated with significant changes in the following circulating factors: tissue inhibitor of metalloproteinase-type 1, leukemia inhibitory factor 1, C-reactive protein, apolipoprotein A1, fibroblast growth factor 2, serum glutamic oxaloacetic transaminase, macrophage-derived chemokine, and monocyte chemoattractant protein-3. Clenbuterol treatment in the MLP−/− model of heart failure did not rescue heart function, yet did increase CD31+ cells in the bone marrow. This is the first evidence that a beta 2 agonist increases EPC proliferation in the bone marrow in a preclinical model of heart failure.

Keywords

Clenbuterol Heart Failure Muscle LIM Protein Beta 2 Adrenergic Receptor Endothelial Progenitor Cell 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • James E. Rider
    • 1
  • Sean P. Polster
    • 1
  • Sangjin Lee
    • 1
  • Nathan J. Charles
    • 1
  • Neeta Adhikari
    • 1
  • Ami Mariash
    • 1
  • George Tadros
    • 1
  • Jenna Stangland
    • 1
  • Ryszard T. Smolenski
    • 2
  • Cesare M Terracciano
    • 2
  • Paul J.R. Barton
    • 2
  • Emma J. Birks
    • 2
  • Magdi H. Yacoub
    • 2
  • Leslie W. Miller
    • 3
  • Jennifer L. Hall
    • 1
  1. 1.Lillehei Heart InstituteUniversity of MinnesotaMinneapolisUSA
  2. 2.Heart Science Centre, National Heart and Lung InstituteImperial College LondonHarefieldUK
  3. 3.Washington Hospital Center and Georgetown UniversityWashingtonUSA

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