| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Differing from other proliferative cells, myocardial cells are enlarged in response to various stimuli. Therefore, the enlargement of myocardial cells results in systolic heart failure because the heart is an aggregate of myocardial cells. Since heart failure is a common terminal image of various heart diseases such as hypertensive heart disease, sudden cardiomyopathy, and ischemic heart diseases, the treatment of heart failure may be extremely important in the clinical setting. Previous studies have clarified that nerves, body fluid, and endocrine factors in the sympathetic nervous system, renin-angiotensin system, and endothelin system are activated under conditions of stress. These factors bind to the respective receptors on the myocardial cell membrane, and the stimulation is finally transferred to the myocardial cell nucleus via various intracellular information transfer systems. When certain transcriptional control factors are activated in the cell nucleus, myocardial cells change their gene expression patterns from the adult type to the fetal type. These changes are commonly observed during myocardial cell enlargement induced by various factors, and are closely associated with myocardial dysfunction. Therefore, detailed analysis of this intranuclear information transfer system is very useful for elucidating the mechanism of heart failure at the cellular and molecular levels, as well as for developing basic therapeutic tactics for heart failure. We established a method of analyzing a promoter element that responds to pressure overload in vivo by directly injecting the gene into the adult rat myocardium for the first time. As the result of detailed evaluation, we found that GATA transcriptional factors play central roles in the gene expression control during myocardial cell enlargement, and that p300, a transcriptional core activator, is also involved in the transcription of the myocardial gene after binding to GATA factors.
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