Extracellular vesicles as mediators of vascular inflammation in kidney disease.
Extracellular vesicles as mediators of vascular inflammation in kidney disease.
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DOI：
10.5527/wjn.v5.i2.125
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发表时间：
2016-03-06
期刊：
影响因子：
--
通讯作者：
von Vietinghoff, Sibylle
中科院分区：
文献类型：
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作者：
Helmke, Alexandra;von Vietinghoff, Sibylle
血管炎症是肾损害的常见原因，也是肾病患者发病率和死亡率的主要原因。目前的研究一致表明，急性血管炎和动脉粥样硬化患者的细胞外囊泡（EV）增加。最近的研究已经阐明了介导血管壁白细胞聚集和分化的机制。本文探讨了电动汽车在这一过程中的作用。本综述的第一部分讨论了EV在肾血管炎中的功能作用。大多数已发表的数据涉及抗中性粒细胞胞浆抗体（ANCA）相关血管炎，并表明活动性疾病中EV（主要为血小板源性）的数量增加。通过ANCA激活中性粒细胞产生的EV可导致血管损伤。虽然EV在其他类型的自身免疫性血管炎中也升高，如系统性红斑狼疮，但血管内血栓形成以外的功能后果仍有待确定。在典型的溶血性尿毒综合征继发于产滋贺毒素的大肠杆菌感染，EV数升高，并有助于毒素分布到血管壁。第二部分阐述了EV如何调节动脉粥样硬化中的血管炎症的机制，这是一个在尿毒症中加重的过程。在一些对有和无肾脏疾病的患者进行的研究中，循环内皮EV数量增加与动脉粥样硬化并发症相关。尿毒症内皮EV在诱导血管舒张方面存在缺陷。神经元粘附和迁移以及血管内血栓形成受到EV的关键调节，这是一个适合治疗干预的过程。EV可以增强单核细胞与内皮的粘附，并调节巨噬细胞分化和细胞因子产生，对斑块中的局部炎症环境产生主要影响。它们显著影响单核吞噬细胞的脂质吞噬作用和抗原呈递。最后，血小板、红细胞和单核细胞EV在形成适应性T细胞免疫中合作。未来的研究需要确定尿毒症EV的变化及其对血管壁炎性白细胞的不同影响。
Vascular inflammation is a common cause of renal impairment and a major cause of morbidity and mortality of patients with kidney disease. Current studies consistently show an increase of extracellular vesicles (EVs) in acute vasculitis and in patients with atherosclerosis. Recent research has elucidated mechanisms that mediate vascular wall leukocyte accumulation and differentiation. This review addresses the role of EVs in this process. Part one of this review addresses functional roles of EVs in renal vasculitis. Most published data address anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and indicate that the number of EVs, mostly of platelet origin, is increased in active disease. EVs generated from neutrophils by activation by ANCA can contribute to vessel damage. While EVs are also elevated in other types of autoimmune vasculitis with renal involvement such as systemic lupus erythematodes, functional consequences beyond intravascular thrombosis remain to be established. In typical hemolytic uremic syndrome secondary to infection with shiga toxin producing Escherichia coli, EV numbers are elevated and contribute to toxin distribution into the vascular wall. Part two addresses mechanisms how EVs modulate vascular inflammation in atherosclerosis, a process that is aggravated in uremia. Elevated numbers of circulating endothelial EVs were associated with atherosclerotic complications in a number of studies in patients with and without kidney disease. Uremic endothelial EVs are defective in induction of vascular relaxation. Neutrophil adhesion and transmigration and intravascular thrombus formation are critically modulated by EVs, a process that is amenable to therapeutic interventions. EVs can enhance monocyte adhesion to the endothelium and modulate macrophage differentiation and cytokine production with major influence on the local inflammatory milieu in the plaque. They significantly influence lipid phagocytosis and antigen presentation by mononuclear phagocytes. Finally, platelet, erythrocyte and monocyte EVs cooperate in shaping adaptive T cell immunity. Future research is needed to define changes in uremic EVs and their differential effects on inflammatory leukocytes in the vessel wall.