GCSF Partially Repairs Heart Damage Induced by Repetitive β-adrenergic Stimulation in Mice: Potential Role of the Mobilized Bone Marrow-derived Cells

Background: Granulocyte Colony Stimulating Factor (GCSF) repairs acute heart damage.The main mechanism is its direct action on cardiac tissue.However, the role of the mobilized bone marrow-derived cells by GCSF is less explored.Pathologies such as obesity, mental stress and hypertension trigger chronic heart diseases through stimulation of the $-adrenergic system.Therefore, the effect of GCSF and of isolated mobilized blood marrow cells in a mouse model of heart damage induced by repeated β-adrenergic stimulation with isoproterenol was evaluated.Materials and Methods: Two experimental approaches were used: (1) Endogenous mobilization with GCSF was achieved directly in mice with heart damage (5 mg kgG 1 dayG 1 , 7 days, s.c.).( 2) Mobilized bone marrow-derived cells were isolated, labeled and inoculated to other mice with heart damage 1 and 30 days after damage.Ventricular hypertrophy, fibrosis, heart rate and mean blood pressure were measured.Inoculated cells were tracked in the heart.Results: GCSF reduced fibrosis; while, inoculated cells diminished fibrosis and mean blood pressure.Inoculation 30 days post-damage reduced fibrosis even more.Ventricular hypertrophy and heart rate were not restored with any treatment.Inoculated bone marrow-derived cells which were enriched in hematopoietic stem and progenitor cells migrated to the area of damage and some were "SMA-positive.Conclusion: GCSF partially restores heart damage produced by the repetitive β-adrenergic stimulation.Some mobilized bone marrow-derived cells migrate to the area of damage and are "SMA-positive, a phenotype related to cardiac sarcomerogenesis, cardiac muscle differentiation and cardiomyocyte rhythm, which could contribute to their beneficial effect.However, other mechanisms that could also be synergistically acting remain to be studied.A pool containing a diversity of cell types mobilized by GCSF, diminishes fibrosis and blood pressure in hearts damaged by repetitive stimulation of the β-adrenergic system, independently from the presence of the factor.Stimulation of this system is found in conditions such as obesity, metabolic syndrome or hypertension.Therefore, through this mechanism of GCSF, there exists the possibility of restoration of heart damage by mobilizing a pool of easily accessible cells with the factor, without having to isolate particular cell types nor having to expose the patients to invasive procedures.