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Enhanced stem cell migration mediated by VCAM-1/VLA-4 interaction improves cardiac function in virus-induced dilated cardiomyopathy
- Source :
- Basic research in cardiology. 108(6)
- Publication Year :
- 2013
-
Abstract
- Endogenous circulation of bone marrow-derived cells (BMCs) was observed in patients with dilated cardiomyopathy (DCM) who showed cardiac upregulation of Vascular Cell Adhesion Protein-1 (VCAM-1). However, the underlying pathophysiology is currently unknown. Thus, we aimed to analyze circulation, migration and G-CSF-based mobilization of BMCs in a murine model of virus-induced DCM. Mice with coxsackievirus B3 (CVB3) induced DCM and healthy controls were analyzed regarding their myocardial homing factors by PCR. To determine cardiac VCAM-1 expression ELISA and immunohistochemistry were applied. Flow cytometry was performed to analyze BMCs. Cardiac diameters and function were evaluated by echocardiography before and 4 weeks after G-CSF treatment. In murine CVB3-induced DCM an increase of BMCs in peripheral blood and a decrease of BMCs in bone marrow was observed. We found an enhanced migration of Very Late Antigen-4 (VLA-4⁺) BMCs to the diseased heart overexpressing VCAM-1 and higher numbers of CD45⁻CD34⁻Sca-1⁺ and CD45⁻CD34⁻c-kit⁺ cells. Mobilization of BMCs by G-CSF boosted migration along the VCAM-1/VLA-4 axis and reduced apoptosis of cardiomyocytes. Significant improvement of cardiac function was detected by echocardiography in G-CSF-treated mice. Blocking VCAM-1 by a neutralizing antibody reduced the G-CSF-dependent effects on stem cell migration and cardiac function. This is the first study showing that in virus-induced DCM VCAM-1/VLA-4 interaction is crucial for recruitment of circulating BMCs leading to beneficial anti-apoptotic effects resulting in improved cardiac function after G-CSF-induced mobilization.
- Subjects :
- Cardiac function curve
Cardiomyopathy, Dilated
Pathology
medicine.medical_specialty
Physiology
Cardiomyopathy
Coxsackievirus Infections
Vascular Cell Adhesion Molecule-1
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Biology
Integrin alpha4beta1
Real-Time Polymerase Chain Reaction
Flow cytometry
chemistry.chemical_compound
Mice
Downregulation and upregulation
Cell Movement
Physiology (medical)
Granulocyte Colony-Stimulating Factor
medicine
Animals
Humans
VCAM-1
medicine.diagnostic_test
Stem Cells
Dilated cardiomyopathy
medicine.disease
Flow Cytometry
Immunohistochemistry
Disease Models, Animal
medicine.anatomical_structure
chemistry
Echocardiography
Immunology
cardiovascular system
Bone marrow
Stem cell
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 14351803
- Volume :
- 108
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Basic research in cardiology
- Accession number :
- edsair.doi.dedup.....07e1056766c9dfcff95b30ce607a7cde