Abstract 9370: Therapy With Granulocyte Colony-Stimulating Factor in the Chronic Stage, but not in the Acute Stage, Accelerates Healing Process via Nitric Oxide in Experimental Autoimmune Myocarditis in Rats
Purpose: Granulocyte colony-stimulating factor (G-CSF) could mobilize multipotent progenitor cells from bone marrow into peripheral blood, and may improve ventricular function and remodeling after myocardial injury. We investigated serial efficacy of G-CSF therapy upon experimental autoimmune myocarditis in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of cardiac function and tissue regeneration.
Methods: A rat model of porcine myosin-induced myocarditis was used. After the immunization of myosin, G-CSF (10μg/kg/day) or saline was injected intraperitoneally daily on days 0–21 in Experiment I and on days 21- 42 in Experiment II. Additional myosin-immunized rats were orally given with 25 mg/kg/day of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment. At the end of each experiment, hemodynamic study by echocardiography and pathologic study were performed (each group; n=15–20).
Results: In Experiment I, G-CSF treatment with and without L-NAME aggravated cardiac pathology associated with enhanced G-CSF receptor expression and superoxide production. Compared with saline injection in Experiment II, G-CSF treatment significantly improved not only the severity of myocarditis with enhanced von Willebrand factor and vascular endothelial growth factor expression, less myocardial macrophage infiltration, and less myocardial fibrosis but also left ventricular ejection fraction associated with lower heart weight/body weight ratio. In the rats with myocarditis treated with G-CSF associated with oral L-NAME treatment in Experiment II, the severity of myocarditis was not reduced, and the cardiac function was not improved. Myocardial c-kit+ cells were demonstrated only in G-CSF treated group in Experiment II, but not in other groups.
Conclusions: G-CSF has differential effects on experimental autoimmune myocarditis with time. The overwhelming superoxide production by G-CSF administration in the acute stage may fail to improve the condition. G-CSF therapy improved cardiac function in the chronic stage, through the acceleration of healing process and myocardial regeneration via NO system.
- © 2010 by American Heart Association, Inc.