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Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease
BACKGROUND: Kawasaki disease (KD) is an acute vasculitis that may result in permanent coronary artery damage with unknown etiology. Endothelial cell (EC) dysfunction and platelet hyperactivity are the hallmarks of KD. Platelets are involved in the development of endothelial dysfunction. MiR-223 tran...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379370/ https://www.ncbi.nlm.nih.gov/pubmed/35983051 http://dx.doi.org/10.3389/fimmu.2022.922868 |
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author | Guo, Manli Fan, Shunyang Chen, Qian Jia, Cuiping Qiu, Miaoyun Bu, Yun Tang, Wai Ho Zhang, Yuan |
author_facet | Guo, Manli Fan, Shunyang Chen, Qian Jia, Cuiping Qiu, Miaoyun Bu, Yun Tang, Wai Ho Zhang, Yuan |
author_sort | Guo, Manli |
collection | PubMed |
description | BACKGROUND: Kawasaki disease (KD) is an acute vasculitis that may result in permanent coronary artery damage with unknown etiology. Endothelial cell (EC) dysfunction and platelet hyperactivity are the hallmarks of KD. Platelets are involved in the development of endothelial dysfunction. MiR-223 transferred by platelet microparticles (PMPs) has been found to involve in the functional regulation of endothelial cells in sepsis. However, the role of platelet-derived miR-223 in endothelial dysfunction has not yet been investigated in KD. OBJECTIVES: We seek to investigate the role of platelet-derived miR-223 in endothelial dysfunction of KD vasculopathy. METHODS AND RESULTS: Forty-five acute KD patients and 45 matched controls were randomly recruited in the study. When co-cultured with human coronary artery endothelial cells (HCAECs), KD platelets with higher levels of miR-223 were incorporated into HCAECs, resulting in the horizontal transfer of miR-223. Using KD platelets, PMPs, and platelet-releasate from the same amount of blood co-cultured with HCAECs, we found the increased expression of miR-223 in HCAECs was primarily derived from KD platelets, rather than PMPs or free miRNAs from platelet- releasate. KD platelet-derived miR-223 attenuated TNF-α induced intercellular cell adhesion molecule-1 (ICAM-1) expression in HCAECs. KD platelet-derived miR-223 also suppressed the monocyte adhesion to HCAECs. In vivo, platelet-specific miR-223 knockout (PF4-cre: miR-223(flox/flox)) C57BL/6 mice and miR-223(flox/flox) C57BL/6 mice were used. Using Lactobacillus casei cell wall extract (LCWE) to establish KD murine model, we showed that in LCWE-injected PF4-cre: miR-223(flox/flox) mice, deficiency of platelet-miR-223 exacerbates the medial thickening of the abdominal aorta, increased ICAM-1 expression with concomitant CD45(+) inflammatory cells infiltration into the endothelium compared to LCWE-injected miR-223(flox/flox) mice. CONCLUSIONS: The horizontal transfer of platelet-derived miR-223 suppresses the expression of ICAM-1 in HCAECs, which at least in part attenuates leukocyte adhesion, thereby reducing endothelial damage in KD vasculitis |
format | Online Article Text |
id | pubmed-9379370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93793702022-08-17 Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease Guo, Manli Fan, Shunyang Chen, Qian Jia, Cuiping Qiu, Miaoyun Bu, Yun Tang, Wai Ho Zhang, Yuan Front Immunol Immunology BACKGROUND: Kawasaki disease (KD) is an acute vasculitis that may result in permanent coronary artery damage with unknown etiology. Endothelial cell (EC) dysfunction and platelet hyperactivity are the hallmarks of KD. Platelets are involved in the development of endothelial dysfunction. MiR-223 transferred by platelet microparticles (PMPs) has been found to involve in the functional regulation of endothelial cells in sepsis. However, the role of platelet-derived miR-223 in endothelial dysfunction has not yet been investigated in KD. OBJECTIVES: We seek to investigate the role of platelet-derived miR-223 in endothelial dysfunction of KD vasculopathy. METHODS AND RESULTS: Forty-five acute KD patients and 45 matched controls were randomly recruited in the study. When co-cultured with human coronary artery endothelial cells (HCAECs), KD platelets with higher levels of miR-223 were incorporated into HCAECs, resulting in the horizontal transfer of miR-223. Using KD platelets, PMPs, and platelet-releasate from the same amount of blood co-cultured with HCAECs, we found the increased expression of miR-223 in HCAECs was primarily derived from KD platelets, rather than PMPs or free miRNAs from platelet- releasate. KD platelet-derived miR-223 attenuated TNF-α induced intercellular cell adhesion molecule-1 (ICAM-1) expression in HCAECs. KD platelet-derived miR-223 also suppressed the monocyte adhesion to HCAECs. In vivo, platelet-specific miR-223 knockout (PF4-cre: miR-223(flox/flox)) C57BL/6 mice and miR-223(flox/flox) C57BL/6 mice were used. Using Lactobacillus casei cell wall extract (LCWE) to establish KD murine model, we showed that in LCWE-injected PF4-cre: miR-223(flox/flox) mice, deficiency of platelet-miR-223 exacerbates the medial thickening of the abdominal aorta, increased ICAM-1 expression with concomitant CD45(+) inflammatory cells infiltration into the endothelium compared to LCWE-injected miR-223(flox/flox) mice. CONCLUSIONS: The horizontal transfer of platelet-derived miR-223 suppresses the expression of ICAM-1 in HCAECs, which at least in part attenuates leukocyte adhesion, thereby reducing endothelial damage in KD vasculitis Frontiers Media S.A. 2022-08-02 /pmc/articles/PMC9379370/ /pubmed/35983051 http://dx.doi.org/10.3389/fimmu.2022.922868 Text en Copyright © 2022 Guo, Fan, Chen, Jia, Qiu, Bu, Tang and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Guo, Manli Fan, Shunyang Chen, Qian Jia, Cuiping Qiu, Miaoyun Bu, Yun Tang, Wai Ho Zhang, Yuan Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title | Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title_full | Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title_fullStr | Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title_full_unstemmed | Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title_short | Platelet-derived microRNA-223 attenuates TNF-α induced monocytes adhesion to arterial endothelium by targeting ICAM-1 in Kawasaki disease |
title_sort | platelet-derived microrna-223 attenuates tnf-α induced monocytes adhesion to arterial endothelium by targeting icam-1 in kawasaki disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379370/ https://www.ncbi.nlm.nih.gov/pubmed/35983051 http://dx.doi.org/10.3389/fimmu.2022.922868 |
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