Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease.
Disruption of Endothelial Cell Homeostasis Plays a Key Role in the Early Pathogenesis of Coronary Artery Abnormalities in Kawasaki Disease.
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DOI：
10.1038/srep43719
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Kawano Y
中科院分区：
文献类型：
--
作者：
Ueno K;Ninomiya Y;Hazeki D;Masuda K;Nomura Y;Kawano Y
内皮细胞稳态的破坏可能与川崎病（KD）冠状动脉异常（CAA）的发病机制有关。我们试图阐明内皮细胞存活和死亡在KD血管炎中的致病作用。与细菌感染患者的血清相比，KD患者血清刺激的人脐静脉内皮细胞（HUVECs）表现出细胞毒性、高迁移率的组盒蛋白1 （HMGB-1）和caspase-3/7显著增加，磷酸化Akt/Akt （pAkt/Akt）比例降低。与未治疗的HUVECs相比，免疫球蛋白（IG）治疗的KD患者血清刺激HUVECs的细胞毒性、HMGB-1和caspase-3/7水平显著降低，pAkt/Akt比值显著升高（P < 0.001, P = 0.008, P = 0.040和P < 0.001）。在KD患者血清刺激的HUVECs中，IG治疗后细胞毒性水平的升高和pAkt/Akt比值的抑制与CAA的发展密切相关（P = 0.002和P = 0.035）。我们的数据显示，将平衡转向细胞死亡而不是存活似乎扰乱了内皮细胞的稳态，并与CAA的发展密切相关。IG处理的细胞保护作用似乎可以改善内皮细胞的稳态。
Disruption of endothelial cell homeostasis may be associated with the pathogenesis of coronary artery abnormalities (CAA) in Kawasaki disease (KD). We sought to clarify the poorly understood pathogenic role of endothelial cell survival and death in KD vasculitis. Human umbilical vein endothelial cells (HUVECs) stimulated with sera from KD patients, compared with sera from patients with bacterial infections, exhibited significant increases in cytotoxicity, high mobility group box protein 1 (HMGB-1), and caspase-3/7 and a decrease in phosphorylated Akt/Akt (pAkt/Akt) ratios. HUVECs stimulated with sera from KD patients treated with immunoglobulin (IG) showed significantly decreased cytotoxicity, HMGB-1, and caspase-3/7 levels and increased pAkt/Akt ratios, as compared with results for untreated HUVECs (P < 0.001, P = 0.008, P = 0.040, and P < 0.001, respectively). In HUVECs stimulated with sera from KD patients, the increased cytotoxicity levels and the suppression of increased pAkt/Akt ratios after subsequent IG treatment were closely related to the development of CAA (P = 0.002 and P = 0.035). Our data reveal that shifting the balance toward cell death rather than survival appears to perturb endothelial cell homeostasis and is closely related to the development of CAA. The cytoprotective effects of IG treatment appear to ameliorate endothelial cell homeostasis.