Production and Signaling Mechanism of Adorenomedullin in Cardiovascular Cells
心血管细胞中肾上腺髓质素的产生和信号机制
基本信息
- 批准号:10218212
- 负责人:
- 金额:$ 40.83万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research on Priority Areas
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
肾上腺髓质素(AM)是从人嗜铬细胞瘤组织中分离的一种有效的血管舒张肽。AM在心脏和血管壁细胞中高表达,AM在心血管疾病中可能起重要作用,本课题研究了AM的基因表达和分泌,并探讨了AM在心力衰竭和肺动脉高压中的病理生理意义。1)在内毒素休克或心肌梗死模型动物中,心血管组织中AM基因表达明显上调,AM可能是这些疾病中抗损伤的因素之一。2)缺氧条件下心肌细胞AM分泌增加可能与氧化应激有关。心肌细胞分泌的AM可能以自分泌的方式发挥细胞保护作用。3)缺血再灌注期间AM灌注可减轻大鼠左室重构和心肌纤维化的发生。AM的心脏保护作用可能至少部分归因于其抗凋亡作用。4)在人体研究中,静脉输注AM对充血性心力衰竭或毛细血管前肺动脉高压患者具有有益的血液动力学和激素作用。AM及其药物配体在心血管疾病的治疗中应被证明是有用的。
项目成果
期刊论文数量(65)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
T.Shindo, et al.: "Hypotension and resistance to lipopolysaccharide-induced shock in transgenic mice overexpressing adrenomedullin in their vasculature."Circulation. 101. 2309-2316 (2000)
T.Shindo 等人:“在血管系统中过度表达肾上腺髓质素的转基因小鼠中的低血压和对脂多糖诱导的休克的抵抗力。”循环。
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Morimoto A., et al.: "Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats"Hypertension. 33. 1146-1152 (1999)
Morimoto A.等人:“大鼠心室肾上腺髓质素水平与心脏肥大程度相关”高血压。
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Okumura H., et al.: "Adrenomedullin infusion during ischemia/reperfusion attenuates left ventricular remodeling and myocardial fibrosis in rats"Hypertens. Res.. 26 Suppl. S99-104 (2003)
Okumura H.等人:“缺血/再灌注期间的肾上腺髓质素输注可减轻大鼠的左心室重塑和心肌纤维化”。
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T.Shindo, et al.: "Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene"Circulation. 104. 1964-1971 (2001)
T.Shindo 等人:“缺乏肾上腺髓质素基因的小鼠的血管异常和血压升高”循环。
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F.Yoshihara, et al.: "Possible involvement of oxidative stress in hypoxia-induced adrenomedullin secretion in cultured rat cardiomyocytes"Eur.J.Pharmacol.. 436. 1-6 (2002)
F.Yoshihara 等人:“氧化应激可能参与培养大鼠心肌细胞缺氧诱导的肾上腺髓质素分泌”Eur.J.Pharmacol.. 436. 1-6 (2002)
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KANGAWA Kenji其他文献
KANGAWA Kenji的其他文献
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{{ truncateString('KANGAWA Kenji', 18)}}的其他基金
Studies for identification and physiological functions of novel endogenous ligands for G-protein coupled orphan receptors.
G 蛋白偶联孤儿受体新型内源配体的鉴定和生理功能研究。
- 批准号:
13854018 - 财政年份:2001
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for Scientific Research (S)
Molecular Endocrinological Studies of Adrenomedullin in Cardiovascular
心血管肾上腺髓质素的分子内分泌学研究
- 批准号:
10470228 - 财政年份:1998
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The studies for expression and secretion of adrenomedullin and its signal transduction.
肾上腺髓质素的表达、分泌及其信号转导的研究。
- 批准号:
08457269 - 财政年份:1996
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The studies for expression and secretion of adrenomedullin and characterzation of its receptors.
肾上腺髓质素表达和分泌及其受体表征的研究。
- 批准号:
06454344 - 财政年份:1994
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Systematic search on a smooth muscle stimulant peptide in mammalian kidney.
哺乳动物肾脏中平滑肌刺激肽的系统搜索。
- 批准号:
04454566 - 财政年份:1992
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Studies on the processing and secretion mechanisms of atrial natriuretic peptides (ANP and BNP)
心房钠尿肽(ANP和BNP)加工和分泌机制的研究
- 批准号:
02454510 - 财政年份:1990
- 资助金额:
$ 40.83万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)