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

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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.

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Acknowledgments

The authors wish to thank the staff at Luminex Multi-Analyte Profiles (Rules Based Medicine, Austin, Texas).

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Authors and Affiliations

  1. Lillehei Heart Institute, University of Minnesota, 312 Church Street, Minneapolis, MN, 55455, USA

    James E. Rider, Sean P. Polster, Sangjin Lee, Nathan J. Charles, Neeta Adhikari, Ami Mariash, George Tadros, Jenna Stangland & Jennifer L. Hall

  2. Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield, Middlesex, UK

    Ryszard T. Smolenski, Cesare M Terracciano, Paul J.R. Barton, Emma J. Birks & Magdi H. Yacoub

  3. Washington Hospital Center and Georgetown University, Washington, DC, 20010, USA

    Leslie W. Miller

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  1. James E. Rider
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Correspondence to Jennifer L. Hall.

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James E. Rider and Sean P. Polster contributed equally.

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Rider, J.E., Polster, S.P., Lee, S. et al. Chronic Treatment with Clenbuterol Modulates Endothelial Progenitor Cells and Circulating Factors in a Murine Model of Cardiomyopathy. J. of Cardiovasc. Trans. Res. 2, 182–190 (2009). https://doi.org/10.1007/s12265-009-9089-6

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