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

点击翻译按钮获取中文摘要

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.