Modulation of endothelial cell activation in sickle cell disease: a pilot study
Modulation of endothelial cell activation in sickle cell disease: a pilot study
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DOI：
10.1182/blood.v97.7.1937
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发表时间：
2001-04-01
期刊：
影响因子：
20.3
通讯作者：
Hebbel, RP
中科院分区：
文献类型：
--
作者：
Solovey, AA;Solovey, AN;Hebbel, RP
血管壁内皮无疑在镰状细胞病的血管病理学中发挥着重要作用。这项初步研究测试了使用核因子 (NF)-kappaB（一种转录因子）抑制剂来改变这种血管疾病患者内皮激活状态的可行性。在总共 7 次单独的药物暴露测试中，3 名镰状细胞病受试者服用柳氮磺吡啶（每 8 小时口服 1 g），并使用免疫荧光显微镜评估其循环内皮细胞 (CEC) 的激活状态。在镰状细胞转基因小鼠中柳氮磺吡啶，以验证其同时对CEC和血管壁内皮的作用，镰状细胞小鼠的CEC和组织血管壁内皮均具有激活的表型，在这些小鼠中，柳氮磺吡啶显着降低了CEC中血管细胞粘附分子（VCAM）、细胞内粘附分子（ICAM）和E-选择素的表达，并且相应地减少了这些分子在一些组织血管中的表达，在患有镰状细胞病的人类中，柳氮磺吡啶显着降低了 VCAM、ICAM 和 E-选择素的 CEC 表达，但并没有降低组织因子的表达。添加第二种转录因子抑制剂水杨酸并没有改变这一结果。这项初步研究表明，柳氮磺吡啶可以在体内修饰和下调内皮细胞活化状态。(Blood. 2001;97:1937-1941) (C) 2001 by The American血液学会。
The vessel wall endothelium undoubtedly plays a role in the vascular pathobiology of sickle cell disease. This pilot study tested the feasibility of using an inhibitor of nuclear factor (NF)-kappaB, a transcription factor, to modify the endothelial activation state of patients with this vascular disease, For a total of 7 separate drug exposure tests, 3 subjects with sickle cell disease took sulfasalazine (given orally at 1 g every 8 hours), and the activation state of their circulating endothelial cells (CECs) was assessed using immunofluorescence microscopy, Companion studies were also performed using sulfasalazine in sickle transgenic mice to verify its effect simultaneously on both CECs and vessel wall endothelium, Both CECs and tissue vessel wall endothelium in sickle mice have an activated phenotype, In these mice sulfasalazine significantly reduced CEC expression of vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), and E-selectin, and it correspondingly reduced expression of these molecules in some tissue vessels, In humans with sickle cell disease, sulfasalazine significantly reduced CEC expression of VCAM, ICAM, and E-selectin, but it did not reduce expression of tissue factor, Addition of a second transcription factor inhibitor, salsalate, did not change this result, This pilot study suggests that endothelial cell activation state can be modified and down-regulated in vivo by sulfasalazine.(Blood. 2001;97:1937-1941) (C) 2001 by The American Society of Hematology.