Immenschuh S, Schröder H
Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen, Giessen, Germany.
Histol Histopathol. 2006 Jun;21(6):679-85. doi: 10.14670/HH-21.679.
Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-controlling enzyme of heme degradation. HO-1 is up-regulated by a host of oxidative stress stimuli and has potent cytoprotective and anti-inflammatory functions via decreasing tissue levels of the prooxidant heme along with production of bilirubin and the signaling gas carbon monoxide. This review deals with recent findings that highlight the emerging significance of HO-1 in cardiovascular disease. Evidence is presented on how heme and various oxidative stress stimuli may cause endothelial cell dysfunction and how HO-1 may counteract the detrimental effects of oxidative stress in the endothelium. Recent advances in the understanding of the role of endothelial HO-1 for the regulation of the inflammatory response are summarized, including the modulation of leukocyte recruitment and transmigration through the endothelial barrier. Furthermore, experimental evidence from various cell culture and animal models is discussed which suggests an association of HO-1 with the complex sequence of events that cause atherosclerosis. In the second part of the review we present potential strategies that apply HO-1 as a therapeutic target in the treatment of cardiovascular disease. Specific inducers of HO-activity which may ultimately lead to the development of clinically relevant pharmacological applications are introduced.
血红素加氧酶（HO）-1是血红素降解的首个限速酶的诱导型同工酶。HO-1可被多种氧化应激刺激上调，通过降低促氧化剂血红素的组织水平以及产生胆红素和信号气体一氧化碳，发挥强大的细胞保护和抗炎功能。本综述探讨了近期的研究发现，这些发现凸显了HO-1在心血管疾病中的重要性日益显现。文中阐述了血红素和各种氧化应激刺激如何导致内皮细胞功能障碍，以及HO-1如何抵消氧化应激对内皮的有害影响。总结了对内皮HO-1在调节炎症反应中作用的最新认识进展，包括对白细胞通过内皮屏障的募集和迁移的调节。此外，还讨论了来自各种细胞培养和动物模型的实验证据，这些证据表明HO-1与导致动脉粥样硬化的复杂事件序列有关。在综述的第二部分，我们介绍了将HO-1作为治疗靶点用于心血管疾病治疗的潜在策略。引入了可能最终导致临床相关药理学应用发展的HO活性特异性诱导剂。
