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Heme oxygenases, intrinsic defense system, as a novel therapeutic target for atherosclerotic disorders

血红素加氧酶，内在防御系统，作为动脉粥样硬化疾病的新型治疗靶点

基本信息

批准号：
14570682
负责人：
ISHIKAWA Kazunobu
金额：
$ 2.24万
依托单位：
Fukushima Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Heme oxygenase (HO), an enzyme essential for heme degradation, shows anti-oxidative and anti-inflammatory properties via the production of bile pigmehts, carbon monoxide (CO) and ferritin induction under various pathophysiological conditions. A number of recent studies have shown biological effects of HO reaction in cardiovascular disorders. An inducible form of HO, H0-1, is induced by a variety of stresses such as oxidized lipoproteins, cytokines, hemodynamic changes, angiotensin II and nitric oxide (NO) in vascular wall. In this grant period, we observed that H0-1 induction seems to function as an adaptive response against these injurious stimuli. H0-1 induction in artery wall scavenged reactive oxygen species, which leads to the attenuation of monocyte adhesion and chemotaxis. H0-1 induction also reduces lipid peroxidation in plasma and artery wall. These properties of H0-1 suggest anti-atherogenic roles of this enzyme. We also examined the roles of endothelial H0-1 expression and bilirubin in atherogenesis. HO-1 also seems to play a significant role in restenosis after angioplasty, which is a major clinical problem associated with atherosclerosis. As a clinical research, we investigated the changes of the levels of biopyrrins in the patients with acute myocardial infarction. human HO-1 genetics supports these experimental results. We are currently continuing the research, which will solve current problems in various cardiovascular disorders.

血红素加氧酶(HO)是一种血红素降解所必需的酶，在不同的病理生理条件下，通过产生胆汁色素、一氧化碳(CO)和铁蛋白而显示出抗氧化和抗炎的特性。最近的一些研究表明，HO反应在心血管疾病中具有生物学效应。H0-1是一种诱导型HO，由多种应激因素诱导，如氧化的脂蛋白、细胞因子、血流动力学改变、血管紧张素II和血管壁上的一氧化氮(NO)。在这个授权期间，我们观察到H0-1诱导似乎是对这些伤害性刺激的适应性反应。H0-1诱导动脉壁清除活性氧，导致单核细胞黏附和趋化能力减弱。H0-1诱导还可降低血浆和动脉壁的脂质过氧化反应。H0-1的这些特性表明该酶具有抗动脉粥样硬化的作用。我们还研究了内皮H0-1表达和胆红素在动脉粥样硬化形成中的作用。HO-1似乎在血管成形术后的再狭窄中也起着重要作用，这是与动脉粥样硬化相关的一个主要临床问题。作为临床研究，我们观察了急性心肌梗死患者血清生物吡喃水平的变化。人类HO-1基因支持这些实验结果。我们目前正在继续这项研究，这将解决目前各种心血管疾病的问题。