Protective role of heme oxygenase-1 against inflammation in atherosclerosis.
Protective role of heme oxygenase-1 against inflammation in atherosclerosis.
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DOI：
10.2741/3860
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Durante W
中科院分区：
文献类型：
--
作者：
Durante W
血红素加氧酶-1（HO-1）催化游离血红素代谢成等摩尔量的亚铁、一氧化碳（CO）和胆绿素的第一步和限速步骤。胆绿素随后通过胆绿素还原酶转化为胆红素。HO-1是近年来发现的一种治疗血管炎性疾病（包括动脉粥样硬化）的有效靶点。HO-1通过清除促炎分子血红素并通过产生CO和胆色素、胆绿素和胆红素来抑制炎症。这些HO-1反应产物能够通过改变许多免疫细胞（包括内皮细胞、单核细胞/巨噬细胞、树突细胞、T淋巴细胞、肥大细胞和血小板）的活化、分化、成熟和/或极化来阻断先天性和适应性免疫应答。CO和胆色素的这些细胞作用导致白细胞募集和浸润减少，以及动脉粥样硬化病变内促炎介质的产生。本文综述了HO-1抑制动脉粥样硬化血管炎症的机制，并探讨了HO-1及其反应产物可用于改善血管炎症性疾病的可能治疗方式。
Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting step in the metabolism of free heme into equimolar amounts of ferrous iron, carbon monoxide (CO), and biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. HO-1 has recently been identified as a promising therapeutic target in the treatment of vascular inflammatory disease, including atherosclerosis. HO-1 represses inflammation by removing the pro-inflammatory molecule heme and by generating CO and the bile pigments, biliverdin and bilirubin. These HO-1 reaction products are capable of blocking innate and adaptive immune responses by modifying the activation, differentiation, maturation, and/or polarization of numerous immune cells, including endothelial cells, monocytes/macrophages, dendritic cells, T lymphocytes, mast cells, and platelets. These cellular actions by CO and bile pigments result in diminished leukocyte recruitment and infiltration, and pro-inflammatory mediator production within atherosclerotic lesions. This review highlights the mechanisms by which HO-1 suppresses vascular inflammation in atherosclerosis, and explores possible therapeutic modalities by which HO-1 and its reaction products can be employed to ameliorate vascular inflammatory disease.
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