| Project/Area Number |
10218212
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
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Principal Investigator |
KANGAWA Kenji National Cardiovascular Center Research, Institute, Biochemistry, Director, 生化学部, 部長 (00112417)
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| Co-Investigator(Kenkyū-buntansha) |
OKANO Ichiro National Cardiovascular Center Research Institute, Biochemistry, Research Scientist, 生化学部, 室長 (30300974)
KOJIMA Masayasu Kurume University, Institute of Life Science, Molecular Genetics, Professor, 分子生命科学研究所・遺伝子情報部門, 教授 (20202062)
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| Project Period (FY) |
1997 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥63,800,000 (Direct Cost: ¥63,800,000)
Fiscal Year 2002: ¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2001: ¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2000: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 1998: ¥13,100,000 (Direct Cost: ¥13,100,000)
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| Keywords | adrenomedullin (AM) / AM gene expression / cardioprotective effect / anti-apoptotic effect / activation of Akt / oxidative stress / heart failure / pulmonary hypertension / 心筋細胞 / 虚血心筋再灌流障害 / アポトーシス抑制作 / 心筋梗塞サイズ / 急性冠症候群 / アドレノメデユリン(AM) / 心筋線維芽細胞 / 低酸素刺激 / AM分泌 / AM遺伝子発現 / 心不全の治療 / 血管拡張作用 / 肺動脈楔入圧の低下 / 心係数の増加 / 心拍出量増大 / 血漿cAMP / 心後負荷の軽減 / 産生調節 / 急性心筋梗塞 / 培養心筋細胞 / 培養非心筋細胞 / オートクリン / パラクリン / 降圧ペプチド / 遺伝子発現調節 / 培養血管内皮細胞(HAEC) / AM遺伝子のプロモーター / NF-IL6 / 心血管系の局所ホルモン / 敗血症ショック |
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| Research Abstract |
Adrenomedullin (AM) is a potent vasorelaxant peptide isolated from human pheochromocytoma tissue. mRNA of AM is highly expressed in the cells of heart and vascular wall, and AM may play an important role in cardiovascular diseases.
In this project, we have studied the gene expression and secretion of AM, and also examined the pathophysiological significance of AM in heart failure and pulmonary hypertension.
1) In the model animals of endotoxin shock or myocardial infarction, marked induction of AM gene expression was observed in the cardiovascular tissues, and AM may be one of the factors acting against damage in these diseases.
2) An oxidative stress may be involved in the increased AM secretion from cardiac myocytes under hypoxic condition. AM secreted from myocytes may play a cell protective role in an autocrine manner.
3) AM infusion during ischemia/reperfusion attenuated the development of LV remodeling and myocardial fibrosis in rats. The cardioprotective effects of AM may be attributed at least partly to its anti-apoptotic effect.
4) In human studies, intravenous infusion of AM has beneficial haemodynamic and hormonal effects in patients with congestive heart failure or precapillary pulmonary hypertension. AM and its pharmaceutical ligands should prove useful in the treatment of cardiovascular diseases.
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