| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Granulocyte colony-stimulating factor (G-CSF) reportedly stimulates translocation of bone marrow cells into infarcted heart tissue, where they subsequently differentiate into cardiomyocytes, thereby exerting beneficial effects on postinfarction ventricular remodeling and heart function. Whether G-CSF would exert similar effects on hearts with failure of nonischemic origin-e.g., dilated cardiomyopathy (DCM)-remain unknown. UM-X7.1 hamsters are an animal model of human DCM. Beginning at 15 weeks of age, male UM-X7.1 hamsters were subcutaneously injected with G-CSF (10μg/kg/day) 5 days/week for 15 weeks (n=16). A control group (n=15) received an equal volume of distilled water. The G-CSF therapy markedly increased the survival rate among 30-week-old hamsters (100% vs.53%, p<0.0001). This increased survival rate was associated with significantly reduced ventricular enlargement and fibrosis and improved ventricular function (measured in terms of ejection fraction, left ventricular end-diastolic pressure, and ±dp/dt) ; reduced autophagy-like degeneration/death of cardiomyocytes ; decreased membrane permeability (measured in terms of Evans blue uptake) ; downregulation of the cardiotoxic cytokine tumor necrosis factor α-(TNF-α) ; and upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 catalytic activity.
Moreover, confocal microscopy revealed translocation of a relatively small number of bone marrow cells into the myocardium, which then expressed the cardiomyocyte phenotype. In conclusion, G-CSF significantly improves survival rates and cardiac function in an animal model of DCM, suggesting that G-CSF administration may represent a new approach to the prevention of heart failure development resulting from nonischemic cardiomyopathy.
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