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Thromb Res. 2017 Jun;154:96-105. doi: 10.1016/j.thromres.2017.04.016. Epub 2017 Apr 18.

Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response.

Author information

1
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
2
State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
3
State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: zhouzhou@fuwaihospital.org.
4
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: hbyanfuwai@aliyun.com.

Abstract

Platelet activation and endothelial damage play essential roles in atherosclerosis. The pathophysiology of this process is mediated by chemokines and exosomes, two critical players in cell communication. Thrombin-activated platelet-derived exosomes have protective effects on atherosclerosis and endothelial inflammation. To confirm these findings, we isolated exosomes using differential ultracentrifugation and transmission electron microscopy. The exosomes were identified using NanoSight-tracking analysis. Immunofluorescence staining and western blotting were performed to assess exosome uptake and intercellular adhesion molecule-1 (ICAM-1) expression in human umbilical vein endothelial cells (HUVECs). We found that the levels of miR-223, miR-339 and miR-21 were elevated in thrombin-activated platelet exosomes. This finding was verified in our atherosclerosis mouse model. We also found that miR-223 transfection in HUVECs inhibited ICAM-1 expression under TNF-α stimulation. Furthermore, the miR-223 inhibitor blocked the downregulating effects of exosomes on ICAM-1 expression. We examined the key proteins of two classical signaling pathways, MAPK and NF-κB, and found that miR-223 inhibited the phosphorylation of p38, JNK and ERK and blocked the nuclear translocation of NF-κB p65. Our results suggest that thrombin-activated platelet-derived exosomes inhibit ICAM-1 expression during inflammation. MiR-223 may mediate this process via regulation of the NF-κB and MAPK pathways.

KEYWORDS:

Endothelial cell; Exosome; Platelet; Thrombosis; microRNA

PMID:
28460288
DOI:
10.1016/j.thromres.2017.04.016
[Indexed for MEDLINE]

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