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川崎病所致冠状动脉瘤患者血清中血管生成活性受损。

Impairment of angiogenic activity in the serum from patients with coronary aneurysms due to Kawasaki disease.

作者信息

Higashi Kouji, Terai Masaru, Hamada Hiromichi, Honda Takafumi, Kanazawa Masaki, Kohno Yoichi

机构信息

Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

Circ J. 2007 Jul;71(7):1052-9. doi: 10.1253/circj.71.1052.

Abstract

BACKGROUND

The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD.

METHODS AND RESULTS

Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls. In patients with coronary aneurysms, the reduction in the serum angiogenic activity was documented already before KD treatment (p=0.03 vs healthy controls, p=0.08 vs febrile controls) and enhanced after intravenous immune globulin plus aspirin (p<0.001 vs healthy controls, p=0.002 vs febrile controls); both drugs did not affect the assay studied. This reduction was greater in patients who later developed giant aneurysms >8 mm compared with those who developed small to moderate aneurysms (p=0.01). The reduced serum angiogenic activity was partly caused by the reduction in the serum activity of stimulating HUVEC proliferation.

CONCLUSIONS

Serum activity to stimulate HUVEC tube formation was impaired in KD patients who later developed larger coronary aneurysms, which may be associated with the severity of vascular injury.

摘要

背景

炎症介质在川崎病(KD)冠状动脉血管炎的进展中起重要作用,但包括炎症介质在内的KD血清对内皮细胞的影响尚不清楚。我们推测KD患者血清刺激体外人脐静脉内皮细胞(HUVEC)形成管腔的活性可能受损。

方法与结果

与无冠状动脉瘤患者或发热对照者的血清相比,冠状动脉瘤患者的血清刺激HUVEC形成管腔的活性较低。在冠状动脉瘤患者中,血清血管生成活性的降低在KD治疗前就已得到证实(与健康对照相比,p = 0.03;与发热对照相比,p = 0.08),在静脉注射免疫球蛋白加阿司匹林治疗后增强(与健康对照相比,p < 0.001;与发热对照相比,p = 0.002);两种药物均未影响所研究的检测。与发生小至中度动脉瘤的患者相比,后来发生直径>8 mm巨大动脉瘤的患者这种降低更为明显(p = 0.01)。血清血管生成活性降低部分是由于刺激HUVEC增殖的血清活性降低所致。

结论

后来发生较大冠状动脉瘤的KD患者血清刺激HUVEC形成管腔的活性受损,这可能与血管损伤的严重程度有关。

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