| Project/Area Number |
07044253
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAYAMA Shigetake Kyoto University, Faculty of Medicine Professor, 医学研究科, 教授 (70109007)
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| Co-Investigator(Kenkyū-buntansha) |
KELLY Ralph a. Harvard University, Medical School Associate Professor, 医学部, 助教授
SMITH Thomas w. Harvard University, Medical School Professor, 医学部, 教授
MATOBA Yoshiko Kyoto University, Faculty of Medicine Assistant, 医学研究科, 助手 (70239135)
MATSUMORI Akira Kyoto University, Faculty of Medicine Lecturer, 医学研究科, 講師 (70135573)
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| Project Period (FY) |
1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1995: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | cardiac hypertrophy / heart failure / cardiac function / myocyte culture / tumor necrosis factor / cytokine |
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| Research Abstract |
Heart failure is a progressive condition with poor prognosis, and it is accompanied by unnatural myocardial hypertrophy. Altered gene expression in the hypertrophied or failing heart has been identified as being responsible for the progression of the disease. On the other hand, recent evidence has indicated a correlation between the severity of heart failure and the serum concentration of tumor necrosis factor alpha (TNF-alpha), which has a negative inotropic effect. However, it is still unclear whether or not TNF-alpha has a pathogenic role. In this study, using cardiac myocytes from rat neonates, we studied the effects of TNF-alpha in vitro. Quanification of the total cardiac myocyte protein concentration revealed that FCS increased the monocyte protein by 1.52 times compared to that in the serum-free control, and TNF-alpha at the concentration of 1 and 10 ng/ml also increased the protein by 1.24 and 1.18 times, respectively, compared to the control value. The addition of TNF-alpha at 1 and 10 ng/ml increased the ^3H-labeled phenylalanine incorporation by 1.92 and 2.07 times in cardiac myocyte culture respectively, compared to that in the serum-free control. The enhancement of atrial natriuretic peptide gene transcription were 1.21 and 1.72 times control as 1 ng/ml and 10 ng/ml of TNF-alpha respectively, and those of beta-myosin heavy chain gene were 1.17 and 1.37 times control. As a result, it was concluded that THF-alpha promotes myocardial hypertrophy at the transcriptional level, strongly indicating that TNF-alpha accelerates the disease process of heart failure.
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