Cargando…

Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis

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 an...

Descripción completa

Detalles Bibliográficos
Autores principales: Kocatürk, Begüm, Lee, Youngho, Nosaka, Nobuyuki, Abe, Masanori, Martinon, Daisy, Lane, Malcolm E., Moreira, Debbie, Chen, Shuang, Fishbein, Michael C., Porritt, Rebecca A., Franklin, Bernardo S., Noval Rivas, Magali, Arditi, Moshe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443810/
https://www.ncbi.nlm.nih.gov/pubmed/37279077
http://dx.doi.org/10.1172/jci.insight.169855
_version_ 1785093916082569216
author Kocatürk, Begüm
Lee, Youngho
Nosaka, Nobuyuki
Abe, Masanori
Martinon, Daisy
Lane, Malcolm E.
Moreira, Debbie
Chen, Shuang
Fishbein, Michael C.
Porritt, Rebecca A.
Franklin, Bernardo S.
Noval Rivas, Magali
Arditi, Moshe
author_facet Kocatürk, Begüm
Lee, Youngho
Nosaka, Nobuyuki
Abe, Masanori
Martinon, Daisy
Lane, Malcolm E.
Moreira, Debbie
Chen, Shuang
Fishbein, Michael C.
Porritt, Rebecca A.
Franklin, Bernardo S.
Noval Rivas, Magali
Arditi, Moshe
author_sort Kocatürk, Begüm
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10443810
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society for Clinical Investigation
record_format MEDLINE/PubMed
spelling pubmed-104438102023-08-23 Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis Kocatürk, Begüm Lee, Youngho Nosaka, Nobuyuki Abe, Masanori Martinon, Daisy Lane, Malcolm E. Moreira, Debbie Chen, Shuang Fishbein, Michael C. Porritt, Rebecca A. Franklin, Bernardo S. Noval Rivas, Magali Arditi, Moshe JCI Insight Research Article 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. American Society for Clinical Investigation 2023-07-24 /pmc/articles/PMC10443810/ /pubmed/37279077 http://dx.doi.org/10.1172/jci.insight.169855 Text en © 2023 Kocatürk et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kocatürk, Begüm
Lee, Youngho
Nosaka, Nobuyuki
Abe, Masanori
Martinon, Daisy
Lane, Malcolm E.
Moreira, Debbie
Chen, Shuang
Fishbein, Michael C.
Porritt, Rebecca A.
Franklin, Bernardo S.
Noval Rivas, Magali
Arditi, Moshe
Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title_full Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title_fullStr Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title_full_unstemmed Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title_short Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis
title_sort platelets exacerbate cardiovascular inflammation in a murine model of kawasaki disease vasculitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443810/
https://www.ncbi.nlm.nih.gov/pubmed/37279077
http://dx.doi.org/10.1172/jci.insight.169855
work_keys_str_mv AT kocaturkbegum plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT leeyoungho plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT nosakanobuyuki plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT abemasanori plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT martinondaisy plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT lanemalcolme plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT moreiradebbie plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT chenshuang plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT fishbeinmichaelc plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT porrittrebeccaa plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT franklinbernardos plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT novalrivasmagali plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis
AT arditimoshe plateletsexacerbatecardiovascularinflammationinamurinemodelofkawasakidiseasevasculitis