| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Erythropoetin (EPO) is a hypoxia-induced hormone that is essential for normal erythropoiesis and has been broadly used in patients with anemia having a variety of etiology. Recent reports have revealed cardioprotective effects of EPO in the acutely infracted hearts. However, it is unknown whether EPO is effective against cardiomyopathy with chronic heart failure. It was investigated in the present study whether erythropoietin has beneficial effect against cardiomyopathy using hearts with doxorubicin-induced cardiomyopathy, old myocardial infarction and renal failure, and what is the molecular mechanism. The followings were defined.
1. EPO protected left ventricular dilatation, depression of cardiac function, fibrosis and myocyte atropfy with degeneration in doxorubicin-induced cardiomyopathy via protection of down-regulated GATA-4 expression and downregulation of upregulated Cox 2, activation of ERK and expression of depressed EPO receptor. Anti-apoptotic and angiogenetic effects of EPO were independent of the mechanism. The molecular mechanism of the protective effects of granulocyte colony stimulating factor against doxororubicin-induced cardiomyopathy was similar to that in EPO.
2. EPO protected left ventricular remodeling, depressed cardiac function and fibrosis in cardiomyopathy induced by old myocardial infarction and renal failure. The molecular mechanism was reductions of inflammatory cytokine and protection of oxidative damage via activations of Stat3 and Akt, and evpression of EPO receptor. But GATA 4 or Cox-2 was independent of the beneficial effects, in the difference from that in doxororubicin-induced cardiomyopathy model.
3. The above mechanism was confirmed at cultured cardiomyocyte level.
4. In addition to intravenously injected EPO, EPO-immersed gelatin hydrogel sheets showed the beneficial effects on the infracted hearts in rabbits. Therefore, the application of the sheets into cardiomyopathy is expected.
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