Mechanism of coronary artery damage in Kawasaki disease and therapy

川崎病（Kawasaki disease， KD）的特点是弥漫性血管炎，包括冠状动脉瘤和明显的免疫激活，如高水平的肿瘤坏死因子（TNF）。为了确认人类冠状动脉内皮细胞（HCAEC）损伤的可能机制，我们研究了暴露于TNE后，HCAEC和人脐静脉内皮细胞（HUVEC）上粘附分子的表达以及这些内皮细胞趋化因子的产生。KD患者血清中可溶性e选择和可溶性细胞间粘附分子- 1 （ICAM- 1）水平显著高于正常对照组。单核细胞趋化蛋白- 1 （MCP- 1）和白细胞介素-8 （IL-8）在KD血清中显著高于正常对照组。TNF能够增加内皮细胞上的e -选择素和ICAM- I，诱导MCP-1和IL-8的产生。这些发现在华电中得到了显著的认可。综上所述，TNF激活的HCAEC显著表达粘附分子并产生趋化因子，导致冠状动脉内皮白细胞聚集。这些结果提示HEAEC的异常激活可能与冠状动脉病变inKD的发展有关。

Kawasaki disease (KD) is characterized by diffuse vasculitis including coronary artery aneurysm and marked immune activation such as high levels of tumor necrosis factor (TNF). To confirm possible mechnisms of injury to human coronary artery eridothelial cells (HCAEC) we invastigated expression of adhesion molecules on HCAEC as well as human umbilical vein endothelial cells (HUVEC) and production of chemokine by these endothelial cells following exposure to TNE.Levels of soluble E-selection and soluble intercellular adhesion molecule- 1 (ICAM- 1) were significantiy higher in sera from patients with KD than in normal controls. Monocyte chemoattractant protein- 1 (MCP- 1 ) and interleukin-8 (IL-8) were significantly higher in KD sera than in normal controls. TNF was able to increase E-selectin and ICAM- I on endothelial cells, and induce the production of MCP-1 and IL-8. These findings were remarkably recognized in HUAEC.ln summary, HCAEC activated by TNF remarkably expressed adhesion molecules and produced chemokine, resuting leukocyte accumulation in coronary artery endothelium. These findings suggest that abnormal activation of HEAEC may contributeto the development of coronary artery lesions inKD.