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Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.
J Mol Cell Cardiol. 2010 Sep; 49(3):469-81.JM

Abstract

We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20170662

Citation

Shimada, Kana, et al. "Therapy With Granulocyte Colony-stimulating Factor in the Chronic Stage, but Not in the Acute Stage, Improves Experimental Autoimmune Myocarditis in Rats Via Nitric Oxide." Journal of Molecular and Cellular Cardiology, vol. 49, no. 3, 2010, pp. 469-81.
Shimada K, Okabe TA, Mikami Y, et al. Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide. J Mol Cell Cardiol. 2010;49(3):469-81.
Shimada, K., Okabe, T. A., Mikami, Y., Hattori, M., Fujita, M., & Kishimoto, C. (2010). Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide. Journal of Molecular and Cellular Cardiology, 49(3), 469-81. https://doi.org/10.1016/j.yjmcc.2010.02.003
Shimada K, et al. Therapy With Granulocyte Colony-stimulating Factor in the Chronic Stage, but Not in the Acute Stage, Improves Experimental Autoimmune Myocarditis in Rats Via Nitric Oxide. J Mol Cell Cardiol. 2010;49(3):469-81. PubMed PMID: 20170662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide. AU - Shimada,Kana, AU - Okabe,Taka-aki, AU - Mikami,Yu, AU - Hattori,Miki, AU - Fujita,Masatoshi, AU - Kishimoto,Chiharu, Y1 - 2010/02/17/ PY - 2010/01/30/received PY - 2010/02/04/accepted PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/12/14/medline SP - 469 EP - 81 JF - Journal of molecular and cellular cardiology JO - J. Mol. Cell. Cardiol. VL - 49 IS - 3 N2 - We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. SN - 1095-8584 UR - https://www.unboundmedicine.com/medline/citation/20170662/Therapy_with_granulocyte_colony_stimulating_factor_in_the_chronic_stage_but_not_in_the_acute_stage_improves_experimental_autoimmune_myocarditis_in_rats_via_nitric_oxide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(10)00038-6 DB - PRIME DP - Unbound Medicine ER -