Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
Begüm Kocatürk, Youngho Lee, Nobuyuki Nosaka, Masanori Abe, Daisy Martinon, Malcolm E. Lane, Debbie Moreira, Shuang Chen, Michael C. Fishbein, Rebecca A. Porritt, Bernardo S. Franklin, Magali Noval Rivas, and Moshe Arditi
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Published September 25, 2023 - More info
JCI Insight. 2023;8(17):e174463. https://doi.org/10.1172/jci.insight.174463.
© 2023 The American Society for Clinical Investigation
Related article:
Abstract
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.
Authors
Begüm Kocatürk, Youngho Lee, Nobuyuki Nosaka, Masanori Abe, Daisy Martinon, Malcolm E. Lane, Debbie Moreira, Shuang Chen, Michael C. Fishbein, Rebecca A. Porritt, Bernardo S. Franklin, Magali Noval Rivas, Moshe Arditi
Original citation JCI Insight. 2023;8(14):e169855. https://doi.org/10.1172/jci.insight.169855
Citation for this corrigendum: JCI Insight. 2023;8(16):e174463. https://doi.org/10.1172/jci.insight.174463
The correct legend for Figure 2, E and F, is below:
(E and F) IL-6 and TPO levels in the serum of PBS- and LCWE-injected mice (n = 8 to 12 mice/group) at 24 hours and 1 week after LCWE injection.
The related text in the section Increased platelet count during LCWE-induced KD vasculitis has also been corrected. The correct sentence is below:
Similarly, compared with PBS-injected control mice, LCWE-injected mice showed significantly increased levels of circulating levels of IL-6 and TPO at 1 week and 1 day after LCWE, respectively (Figure 2, E and F).
The text in the related section Deletion of c-Mpl inhibits LCWE-induced cardiovascular inflammation has also been corrected. The correct sentence is below:
We found that TPO, which stimulates thrombocytosis, was elevated in LCWE-injected mice (Figure 2F).
The HTML and PDF versions have been updated online.
The authors regret the errors.
