Chronic treatment with clenbuterol modulates endothelial progenitor cells and circulating factors in a murine model of cardiomyopathy.

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.

• Authors: 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
• Journal: Journal of cardiovascular translational research (J Cardiovasc Transl Res) Vol. 2 Issue 2 Pg. 182-90 (Jun 2009) ISSN: 1937-5395 [Electronic] United States
• PMID: 20559986 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-Agonists
• Apolipoprotein A-I
• Biomarkers
• Ccl22 protein, mouse
• Chemokine CCL22
• LIM Domain Proteins
• Leukemia Inhibitory Factor
• Lif protein, mouse
• Muscle Proteins
• Platelet Endothelial Cell Adhesion Molecule-1
• RNA, Messenger
• Receptors, Adrenergic, beta-2
• Tissue Inhibitor of Metalloproteinase-1
• cysteine and glycine-rich protein 3
• Fibroblast Growth Factor 2
• C-Reactive Protein
• Aspartate Aminotransferases
• Carboxypeptidases A
• Cpa3 protein, mouse
• Clenbuterol

Topics

• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-Agonists (administration & dosage, pharmacology)
• Animals
• Apolipoprotein A-I (blood)
• Aspartate Aminotransferases (blood)
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Carboxypeptidases A (blood)
• Cardiomyopathies (blood, drug therapy, genetics, pathology, physiopathology)
• Cell Proliferation (drug effects)
• Chemokine CCL22 (blood)
• Clenbuterol (administration & dosage, pharmacology)
• Disease Models, Animal
• Endothelial Cells (drug effects, immunology, metabolism)
• Fibroblast Growth Factor 2 (blood)
• Gene Expression Regulation
• Injections, Subcutaneous
• LIM Domain Proteins
• Leukemia Inhibitory Factor (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle Proteins (deficiency, genetics)
• Myocardium (metabolism, pathology)
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• RNA, Messenger (metabolism)
• Receptors, Adrenergic, beta-2 (genetics, metabolism)
• Stem Cells (drug effects, immunology, metabolism)
• Stroke Volume
• Time Factors
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Ventricular Function, Left