Pulmonary and Vascular Medicine Branch, National Heart, Lung and Blood Institute and the Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1476, USA.
Br J Haematol. 2010 Mar;148(5):690-701. doi: 10.1111/j.1365-2141.2009.08004.x. Epub 2009 Dec 1.
The breakdown of senescent or defective red blood cells releases red cell contents, especially haemoglobin, which scavenges nitric oxide (NO) and decomposes to haem and free iron. These are potent oxidants, all of which have promoted the evolution of inducible and vasculoprotective compensatory pathways to rapidly clear and detoxify haemoglobin, haem and iron. Chronic haemolytic red cell disorders as diverse as sickle cell disease, thalassaemia, unstable haemoglobinopathy, cytoskeletal defects and enzymopathies have been linked to a clinical constellation of pulmonary hypertension, priapism, leg ulceration and possibly cerebrovascular disease and thrombosis. Besides free haemoglobin, haemolysis has been associated with extracellular arginase that limits substrate availability to NO synthase, endogenous inhibitors of NO synthase activity, and inappropriate activation of haemostatic pathways. This article reviews the haemolytic disorders that have been reported to manifest vascular complications, and explores the speculative possibility that haemolysis mediates some of the vascular complications of inflammation and diabetes.
衰老或有缺陷的红细胞破裂会释放红细胞内容物，特别是血红蛋白，它会清除一氧化氮 (NO) 并分解为血红素和游离铁。这些都是强氧化剂，所有这些都促进了诱导性和血管保护代偿途径的进化，以快速清除和解毒血红蛋白、血红素和铁。慢性溶血性红细胞疾病，如镰状细胞病、地中海贫血、不稳定血红蛋白病、细胞骨架缺陷和酶病，与肺动脉高压、阴茎异常勃起、腿部溃疡以及可能的脑血管疾病和血栓形成的临床综合征有关。除了游离血红蛋白外，溶血还与细胞外的精氨酸酶有关，该酶限制了一氧化氮合酶的底物可用性、一氧化氮合酶活性的内源性抑制剂以及止血途径的不当激活。本文综述了已报道的会出现血管并发症的溶血性疾病，并探讨了溶血可能介导炎症和糖尿病的一些血管并发症的推测性可能性。
