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

血红素加氧酶（HO）是血红素降解所必需的酶，在各种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。HO是一种可诱导的HO，H 0 -1是由氧化脂蛋白、细胞因子、血流动力学变化、血管紧张素II和一氧化氮（NO）等多种应激因素诱导产生的。在此期间，我们观察到，H 0 -1诱导似乎是对这些有害刺激的适应性反应。动脉壁H 0 -1诱导清除活性氧，导致单核细胞粘附和趋化性减弱。H 0 -1诱导还减少血浆和动脉壁中的脂质过氧化。H 0 -1的这些性质表明这种酶的抗动脉粥样硬化作用。我们还研究了内皮细胞H 0 -1表达和胆红素在动脉粥样硬化形成中的作用。HO-1似乎也在血管成形术后再狭窄中发挥重要作用，再狭窄是与动脉粥样硬化相关的主要临床问题。作为临床研究，我们观察了急性心肌梗死患者血清中生物吡啉水平的变化。人类HO-1遗传学支持这些实验结果。我们目前正在继续研究，这将解决目前各种心血管疾病的问题。

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.