title: Clenbuterol plus granulocyte colony-stimulating factor regulates stem/progenitor cell mobilization and exerts beneficial effect by increasing neovascularization in rats with heart failure.
abstract: BACKGROUND
  Treatment of beta2-adrenergic receptor agonists with myeloid cytokines, such as granulocyte colony-stimulating factor (G-CSF) has been reported to enhance stem/progenitor cell mobilization and proliferation in ischemic myocardium. However, whether the combination therapy of G-CSF and clenbuterol (Clen) contributes to improved left ventricular (LV) function remains uncertain. We investigated whether this combination therapy induced bone marrow-derived stem/progenitor cell mobilization, neovascularization, and altered LV function after acute myocardial infarction (MI).
  
  
  RESULTS
  Following MI, rats were treated with single Clen, high-dose Clen, and G-CSF + Clen. We evaluated LV function and remodeling with the use of echocardiography in addition to hemodynamics 3 weeks after MI. Treatment with G-CSF + Clen increased (P < .05), compared with no treatment, LV ejection fraction 46 ± 3% vs 34 ± 2%, LV dP/dt 5,789 ± 394 mm Hg vs 4,503 ± 283 mm Hg, and the percentage of circulating CD34+ cells, appearing to correlate with improvements in LV function.
  
  
  CONCLUSIONS
  Combination therapy improved LV function 3 weeks after MI, suggesting that G-CSF + Clen might augment stem/progenitor cell migration, contributing to tissue healing. These data raise the possibility that enhancing endogenous bone marrow-derived stem/progenitor cell mobilization may be a new treatment for ischemic heart failure after MI.
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona 85723 , USA.
authors.forename: Toshikazu D
authors.initials: TD
authors.lastname: Tanaka
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Lancaster
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juneman
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Bahl
authors.forename: Steven
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D002976:Clenbuterol
keywords: Neovascularization; beta(2)-adrenergic receptor agonist