Lau Denise, Baldus Stephan
Department of Cardiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Pharmacol Ther. 2006 Jul;111(1):16-26. doi: 10.1016/j.pharmthera.2005.06.023. Epub 2006 Feb 13.
Myeloperoxidase (MPO), a heme protein abundantly expressed in polymorphonuclear neutrophils (PMN), has long been viewed to function primarily as a bactericidal enzyme centrally linked to innate host defense. Recent observations now extend this perspective and suggest that MPO is profoundly involved in the regulation of cellular homeostasis and may play a central role in initiation and propagation of acute and chronic vascular inflammatory disease. For example, low levels of MPO-derived hypochlorous acid (HOCl) interfere with intracellular signaling events, MPO-dependent oxidation of lipoproteins modulates their affinity to macrophages and the vessel wall, MPO-mediated depletion of endothelial-derived nitric oxide (NO) impairs endothelium-dependent vasodilatation, and nitrotyrosine (NO(2)Tyr) formation by MPO sequestered into the vessel wall may affect matrix protein structure and function. Future studies are needed to further elucidate the significance of MPO in the development of acute and chronic vascular disease and to evaluate MPO as a potential target for treatment.
髓过氧化物酶（MPO）是一种在多形核中性粒细胞（PMN）中大量表达的血红素蛋白，长期以来一直被认为主要作为一种与先天性宿主防御密切相关的杀菌酶发挥作用。最近的观察结果拓展了这一观点，表明MPO深度参与细胞稳态的调节，并且可能在急性和慢性血管炎性疾病的起始和发展中起核心作用。例如，低水平的MPO衍生的次氯酸（HOCl）会干扰细胞内信号转导事件，MPO依赖的脂蛋白氧化调节其对巨噬细胞和血管壁的亲和力，MPO介导的内皮源性一氧化氮（NO）消耗会损害内皮依赖性血管舒张，而沉积在血管壁中的MPO形成的硝基酪氨酸（NO(2)Tyr）可能会影响基质蛋白结构和功能。需要进一步的研究来阐明MPO在急性和慢性血管疾病发展中的意义，并评估MPO作为潜在治疗靶点的可能性。
