Chronic treatment with clenbuterol modulates endothelial progenitor cells and circulating factors in a murine model of cardiomyopathy.
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.
Rider
James E
JE
Lillehei Heart Institute, University of Minnesota, 312 Church Street, Minneapolis, MN 55455, USA.
Polster
Sean P
SP
Lee
Sangjin
S
Charles
Nathan J
NJ
Adhikari
Neeta
N
Mariash
Ami
A
Tadros
George
G
Stangland
Jenna
J
Smolenski
Ryszard T
RT
Terracciano
Cesare M
CM
Barton
Paul J R
PJ
Birks
Emma J
EJ
Yacoub
Magdi H
MH
Miller
Leslie W
LW
Hall
Jennifer L
JL
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D043422:Carboxypeptidases A / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects*; D054422:Chemokine CCL22 / Q000097:blood; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005786:Gene Expression Regulation; D007279:Injections, Subcutaneous; D060588:LIM Domain Proteins; D053605:Leukemia Inhibitory Factor / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013318:Stroke Volume; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016277:Ventricular Function, Left
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D016632:Apolipoprotein A-I; D015415:Biomarkers; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D060588:LIM Domain Proteins; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D009124:Muscle Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D019715:Tissue Inhibitor of Metalloproteinase-1; C090114:cysteine and glycine-rich protein 3; D016222:Fibroblast Growth Factor 2; D002097:C-Reactive Protein; D001219:Aspartate Aminotransferases; D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse; D002976:Clenbuterol