Attenuation of cardiac hypertrophy by G‐CSF is associated with enhanced migration of bone marrow‐derived cells

• Published in: Journal of cellular and molecular medicine Vol. 19; no. 5; pp. 1033 - 1041
• Main Authors: Huber, Bruno C., Beetz, Nick L., Laskowski, Alexandra, Ziegler, Tilman, Grabmaier, Ulrich, Kupatt, Christian, Herbach, Nadja, Wanke, Ruediger, Franz, Wolfgang‐Michael, Massberg, Steffen, Brunner, Stefan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2015; BlackWell Publishing Ltd
• Subjects: Animals; Aorta; Apoptosis; Apoptosis - drug effects; Atrial Remodeling - drug effects; BMCs; Bone marrow; Bone Marrow Cells - drug effects; Cardiomegaly - physiopathology; Cardiomegaly - prevention & control; Cardiomyopathy; Cell adhesion; Cell adhesion & migration; Cell Movement - drug effects; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Colony-stimulating factor; Coronary vessels; Cytokines; Disease Models, Animal; Echocardiography; Enzyme-linked immunosorbent assay; Eutrophication; Fibrosis; Fibrosis - prevention & control; Flow Cytometry; Gene expression; Gene Expression - drug effects; Granulocyte Colony-Stimulating Factor - pharmacology; Growth factors; G‐CSF; Heart; Heart failure; Homing; Humans; Hypertrophy; Laboratory animals; Leukocytes (granulocytic); Male; Mice, Inbred C57BL; migration; Myocardial infarction; Myocardium; Myocardium - metabolism; Myocardium - pathology; Original; Reverse Transcriptase Polymerase Chain Reaction; Stem cell factor; Stem Cell Factor - genetics; Stem Cell Factor - metabolism; Stem cell transplantation; Stem cells; Survival; Survival Analysis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Ventricular Remodeling - drug effects; United States > US; Germany; migration; fibrosis; BMCs; hypertrophy; G-CSF
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12494

Granulocyte‐colony stimulating factor (G‐CSF) has been shown to promote mobilization of bone marrow‐derived stem cells (BMCs) into the bloodstream associated with improved survival and cardiac function after myocardial infarction. Therefore, the aim of the present study was to investigate whether G‐CSF is able to attenuate cardiac remodelling in a mouse model of pressure‐induced LV hypertrophy focusing on mobilization and migration of BMCs. LV hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6J mice. Four weeks after TAC procedure. Mice were treated with G‐CSF (100 μg/kg/day; Amgen Biologicals) for 2 weeks. The number of migrated BMCs in the heart was analysed by flow cytometry. mRNA expression and protein level of different growth factors in the myocardium were investigated by RT‐PCR and ELISA. Functional analyses assessed by echocardiography and immunohistochemical analysis were performed 8 weeks after TAC procedure. G‐CSF‐treated animals revealed enhanced homing of VLA‐4+ and c‐kit+ BMCs associated with increased mRNA expression and protein level of the corresponding homing factors Vascular cell adhesion protein 1 and Stem cell factor in the hypertrophic myocardium. Functionally, G‐CSF significantly preserved LV function after TAC procedure, which was associated with a significantly reduced area of fibrosis compared to control animals. Furthermore, G‐CSF‐treated animals revealed a significant improvement of survival after TAC procedure. In summary, G‐CSF treatment preserves cardiac function and is able to diminish cardiac fibrosis after induction of LV hypertrophy associated with increased homing of VLA‐4+ and c‐kit+ BMCs and enhanced expression of their respective homing factors VCAM‐1 and SCF.