Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.
Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.
复制标题
在川崎血管炎小鼠模型中，血小板可加重心血管炎症。
DOI：
10.1172/jci.insight.169855
复制
发表时间：
2023-07-24
期刊：
影响因子：
8
通讯作者：
Arditi, Moshe
中科院分区：
文献类型：
--
作者：
Kocaturk, Begum;Lee, Youngho;Nosaka, Nobuyuki;Abe, Masanori;Martinon, Daisy;Lane, Malcolm E.;Moreira, Debbie;Chen, Shuang;Fishbein, Michael C.;Porritt, Rebecca A.;Franklin, Bernardo S.;Rivas, Magali Noval;Arditi, Moshe
川崎病（KD）是儿童获得性心脏病的主要病因。KD过程中观察到血小板计数和活化增加，血小板计数升高与静脉内免疫球蛋白耐药性和冠状动脉瘤的较高风险相关。然而，血小板在KD发病机制中的作用仍不清楚。在这里，我们分析了KD患者全血中产生的转录组学数据，发现了急性KD期间血小板相关基因表达的变化。在KD血管炎的干酪乳杆菌细胞壁提取物（LCWE）小鼠模型中，LCWE注射液增加血小板计数和单核细胞-血小板聚集体（MPA）的形成，上调可溶性P-选择素的浓度，并增加循环血小板生成素和白细胞介素6（IL-6）。此外，血小板计数与心血管炎症的严重程度相关。血小板的遗传耗竭（Mpl-/-小鼠）或用抗CD 42 b抗体治疗显著减少LCWE诱导的心血管病变。此外，在小鼠模型中，血小板通过形成MPA促进血管炎症，这可能会放大IL-1B的产生。总而言之，我们的结果表明血小板活化会加剧KD血管炎小鼠模型中心血管病变的发展。这些发现增强了我们对KD血管炎发病机制的理解，并突出了已知可增强IL-1B产生的MPA作为这种疾病的潜在治疗靶点。
Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Increased platelet counts and activation are observed during the course of KD, and elevated platelet counts are associated with higher risks of developing intravenous immunoglobulin resistance and coronary artery aneurysms. However, the role of platelets in KD pathogenesis remains unclear. Here, we analyzed transcriptomics data generated from the whole blood of patients with KD and discovered changes in the expression of platelet-related genes during acute KD. In the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, LCWE injection increased platelet counts and the formation of monocyte-platelet aggregates (MPAs), upregulated the concentration of soluble P-selectin, and increased circulating thrombopoietin and interleukin 6 (IL-6). Furthermore, platelet counts correlated with the severity of cardiovascular inflammation. Genetic depletion of platelets (Mpl–/– mice) or treatment with an anti-CD42b antibody significantly reduced LCWE-induced cardiovascular lesions. Furthermore, in the mouse model, platelets promoted vascular inflammation via the formation of MPAs, which likely amplified IL-1B production. Altogether, our results indicate that platelet activation exacerbates the development of cardiovascular lesions in a murine model of KD vasculitis. These findings enhance our understanding of KD vasculitis pathogenesis and highlight MPAs, which are known to enhance IL-1B production, as a potential therapeutic target for this disorder.
登录
查看更多内容
影响因子：
3.3
作者：
Eicher JD;Wakabayashi Y;Vitseva O;Esa N;Yang Y;Zhu J;Freedman JE;McManus DD;Johnson AD
通讯作者：
Johnson AD
影响因子：
4.4
作者：
Abe, J;Jibiki, T;Terai, M
通讯作者：
Terai, M
影响因子：
4.3
作者：
Jin, Jing;Wang, Jing;Yu, Haiguo
通讯作者：
Yu, Haiguo
影响因子：
13.6
作者：
Barrett TJ;Cornwell M;Myndzar K;Rolling CC;Xia Y;Drenkova K;Biebuyck A;Fields AT;Tawil M;Luttrell-Williams E;Yuriditsky E;Smith G;Cotzia P;Neal MD;Kornblith LZ;Pittaluga S;Rapkiewicz AV;Burgess HM;Mohr I;Stapleford KA;Voora D;Ruggles K;Hochman J;Berger JS
通讯作者：
Berger JS
影响因子：
24
作者：
Hirono, Keiich;Foell, Dirk;Miyawaki, Toshio
通讯作者：
Miyawaki, Toshio