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- Title
Enhanced stem cell migration mediated by VCAM-1/VLA-4 interaction improves cardiac function in virus-induced dilated cardiomyopathy.
- Authors
Brunner, Stefan; Theiss, Hans D.; Leiss, Monika; Grabmaier, Ulrich; Grabmeier, Johanna; Huber, Bruno; Vallaster, Markus; Clevert, Dirk Andre; Sauter, Martina; Kandolf, Reinhard; Rimmbach, Christian; David, Robert; Klingel, Karin; Franz, Wolfgang-Michael
- 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
STEM cells; CELL migration; INTEGRINS; PATHOLOGICAL physiology; DILATED cardiomyopathy; HEART function tests; B cells; ECHOCARDIOGRAPHY
- Publication
Basic Research in Cardiology, 2013, Vol 108, Issue 6, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-013-0388-3