Mechanism of coronary artery damage in Kawasaki disease and therapy

川崎病冠状动脉损伤机制及治疗

• 批准号: 09670815
• 负责人: FUJIEDA Mikiya
• 金额: $ 0.9万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670815/
• 关键词: Kawasaki disease; coronary artery endothelial cells; coronary artery lesions; adhesion molecule; chemokine; 臍帯静脈由来血菅内皮細胞

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.

川崎（KD）以弥漫性血管炎（包括冠状动脉瘤）和显著的免疫激活（如高水平的肿瘤坏死因子（TNF））为特征。为了证实人冠状动脉内皮细胞（HCAEC）损伤的可能机制，我们研究了在暴露于TNE后HCAEC以及人脐静脉内皮细胞（HUVEC）上粘附分子的表达以及这些内皮细胞的趋化因子的产生。川崎病患者血清中IgG、IgM川崎病患儿血清单核细胞趋化蛋白-1（MCP- 1）和白细胞介素-8（IL-8）水平明显高于正常对照组。TNF能增加内皮细胞上的E-选择素和ICAM-1，并诱导MCP-1和IL-8的产生。总之，TNF激活的HCAEC表达粘附分子，产生趋化因子，导致白细胞在冠状动脉内皮聚集。这些结果表明，HEAEC的异常激活可能与KD冠状动脉病变的发生有关。

项目成果

Fujieda M, Nagata M, Akioka Y, Hattori M, Kawaguchi H, Ito k.: "Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with propylthiouracil therapy." Acta Paediatrica Japonica. 40. 286-289 (1998)

Fujieda M、Nagata M、Akioka Y、Hattori M、Kawaguchi H、Ito k.：“与丙硫氧嘧啶治疗相关的抗中性粒细胞胞质抗体阳性新月体肾小球肾炎。”

Fujieda Mikiya et al: "Antineutrophil cytoplasmic antibody(ANCA)-positive crescentic glomerulonephritis associated with propylthiouracil therapy." Acta Pediatr Jpn. 40. 286-289 (1998)

Fujieda Mikiya 等人：“与丙硫氧嘧啶治疗相关的抗中性粒细胞胞浆抗体 (ANCA) 阳性新月体肾小球肾炎。”

Fujieda Mikiya et al: "Levels of soluble thrombomodulin and of antibodies to bovine glomerular endothelial cells and Henoch-Schonlein purpura." Archives of Disease in Childhood. 77(in press). (1998)

Fujieda Mikiya 等人：“可溶性血栓调节蛋白以及牛肾小球内皮细胞和过敏性紫癜抗体的水平。”

Fujieda Mikiya et al: "Levels of soluble thrombomodulin and of antibodies to bovine glomerular endothelial cells and Henoch-Schonlein purpura." Archives of Disease in Childhood. 78. 240-244 (1998)

Fujieda Mikiya 等人：“可溶性血栓调节蛋白以及牛肾小球内皮细胞和过敏性紫癜抗体的水平。”

Fujieda Mikiya et al: "Antineutrophil cytoplasmic antibody (ANCA)-positive crescentic glomerulonephritis associated with propylthiouracil therapy." Acta Pediatr Jpn. 40. 286-289 (1998)

Fujieda Mikiya 等人：“与丙硫氧嘧啶治疗相关的抗中性粒细胞胞浆抗体 (ANCA) 阳性新月体肾小球肾炎。”