Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease.

IF 2.3 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Journal of Vascular Research Pub Date : 2022-01-01 Epub Date: 2021-12-20 DOI:10.1159/000520717

Hironobu Nakayama, Hiroyasu Inada, Tatsuya Inukai, Kenta Kondo, Kazuyuki Hirai, Tomonari Tsutsumi, Yoshiyuki Adachi, Noriko Nagi-Miura, Naohito Ohno, Koji Suzuki

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引用次数: 0

Abstract

Introduction and objective: Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis.

Methods: An animal model of KD-like vasculitis was created by injecting mice with Candida albicans water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues.

Results: rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels.

Conclusion: These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.

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重组人可溶性血栓调节蛋白抑制川崎病小鼠动脉炎模型。

简介和目的:川崎病(Kawasaki disease, KD)与病因不明的弥漫性和全身性血管炎相关，主要影响婴儿和儿童。静脉注射免疫球蛋白(IVIG)治疗降低了发生冠状动脉瘤的风险，但一些儿童患有抗IVIG的KD，这增加了他们发生冠状动脉损伤的风险。在这里，我们研究了重组人可溶性血栓调节蛋白(rTM)对血管炎小鼠模型冠状动脉炎发展的影响，rTM具有抗凝血、抗炎和细胞保护特性。方法:通过注射白色念珠菌水溶性组分(CAWS)建立小鼠kd样血管炎动物模型。利用该模型研究大鼠心脏组织中白细胞介素(IL)-10、肿瘤坏死因子α (TNF-α)、组织因子(TF) mRNA的表达及组织病理学变化。结果:在CAWS治疗后34天，rTM治疗可显著降低心肌内皮细胞肥厚。此外，mRNA表达分析显示，rTM给药增加心脏IL-10的表达，直到第27天，而TNF-α的表达未受影响。此外，在脾脏中，rTM治疗可使IL-10和TF表达恢复到正常水平。结论:rTM通过上调IL-10抑制caws诱导的血管炎。因此，rTM可能是治疗KD的有效方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.