Thrombotic Microangiopathies: From Animal Models to Human Disease and Cure
Thrombotic Microangiopathies: From Animal Models to Human Disease and Cure
复制标题
DOI：
10.1159/000314579
复制
发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Noris, Marina
中科院分区：
文献类型：
--
作者：
Caprioli, Jessica;Remuzzi, Giuseppe;Noris, Marina
血栓性微血管病是一组微血管疾病，伴有器官灌注量减少和溶血性贫血。血栓性微血管病理性贫血(TMA)的两种最相关的症状是血栓性血小板减少性紫癜(UP)和溶血性尿毒症综合征(HUS)。在TIP中，系统性的血小板微血管聚集会导致大脑和其他器官的缺血。在HUS中，血小板-纤维蛋白血栓主要阻塞肾循环。TTP可由于von Willebrand因子裂解酶(ADAMTS13)活性的缺陷而遗传，或由于针对ADAMTS13的自身抗体的存在而获得。大多数HUS病例继发于产生志贺样毒素的大肠杆菌菌株(STX-HUS)的感染，而所有病例中约有5%-10%被归类为非典型HUS(AHUS)。基因衍生的补体系统调节受损与aHUS有关。新鲜冰冻血浆的输注或交换改善了TMA的预后；然而，没有旨在预防或限制微血管病变过程的特定治疗方法被证明影响TMA的进程。大型哺乳动物、小动物模型、UP基因敲除和转基因小鼠模型以及STX-HUS和aHUS已经被开发出来，并为TMA研究的几乎所有领域做出了杰出贡献。对疾病的主要临床特征以及遗传和/或环境因素在疾病发病机制中的重要性有了更好的了解。这些动物模型还允许建立旨在改善对患者的临床方法以及开发新药和疫苗的方案。版权所有(C)2011 S.Karger AG，巴塞尔
Thrombotic microangiopathies are a group of microvascular disorders, with reduced organ perfusion and hemolytic anemia. The two most relevant conditions characterized by thrombotic microangiopathic anemia (TMA) are thrombotic thrombocytopenic purpura (UP) and hemolytic uremic syndrome (HUS). In TIP, systemic microvascular aggregation of platelets causes ischemia in the brain and other organs. In HUS, platelet-fibrin thrombi predominantly occlude the renal circulation. TTP can be inherited due to deficiencies in the activity of von Willebrand factor cleaving protease (ADAMTS13) or acquired due to the presence of autoantibodies directed against ADAMTS13. The majority of HUS cases are secondary to infections by strains of Escherichia coli that produce Shiga-like toxins (Stx-HUS), while about 5-10% of all cases are classified as atypical HUS (aHUS). Genetically derived impaired regulation of the complement system is associated with aHUS. Infusion or the exchange of fresh frozen plasma have ameliorated the prognosis of TMA; however, no specific therapies aimed at preventing or limiting the microangiopathic process have been proven to affect the course of TMA. Large mammals, small animal models, knockout and transgenic mouse models of UP and both Stx-HUS and aHUS have been developed and have provided outstanding contributions to nearly all areas of TMA research. A better understanding of the key clinical features of the diseases and of the importance of genetic and/or environmental factors involved in the pathogenesis of the diseases have been obtained. These animal models have also allowed the set up of protocols aimed at ameliorating the clinical approach to patients and for the development of new drugs and vaccines. Copyright (C) 2011 S. Karger AG, Basel