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

Huber, Bruno C.; Beetz, Nick L.; Laskowski, Alexandra; Ziegler, Tilman; Grabmaier, Ulrich; Kupatt, Christian; Herbach, Nadja; Wanke, Rüdiger; Franz, Wolfgang-Michael; Massberg, Steffen and Brunner, Stefan (2015): Attenuation of cardiac hypertrophy by G-CSF is associated with enhanced migration of bone marrow-derived cells. In: Journal of Cellular and Molecular Medicine, Vol. 19, No. 5: pp. 1033-1041

Abstract

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. Fourweeks after TAC procedure. Mice were treated with G-CSF (100g/kg/day;Amgen Biologicals) for 2weeks. 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 8weeks 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.

• Item Type: Journal article
• Faculties: Medicine > Walther Straub Institute of Pharmacology and toxicology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1582-4934
• Language: English