University of Oulu

Horioka, K., Tanaka, H., Okaba, K., Yamada, S., Hayakawa, A., Ishii, N., Motomura, A., Inoue, H., Takauji, S., Isozaki, S., Ogawa, K., Yajima, D., Druid, H., Pakanen, L., & Porvari, K. (2023). Bioprotective role of platelet-derived microvesicles in hypothermia: Insight into the differential characteristics of peripheral and splenic platelets. Thrombosis Research, 223, 155–167.

Bioprotective role of platelet-derived microvesicles in hypothermia : insight into the differential characteristics of peripheral and splenic platelets

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Author: Horioka, Kie1,2,3; Tanaka, Hiroki4; Okaba, Keisuke3;
Organizations: 1Department of Forensic Medicine, Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland
2Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
3Department of Legal Medicine, International University of Health and Welfare, Narita, Japan
4Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan
5Department of Anatomy, International University of Health and Welfare, Narita, Japan
6Department of Legal Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
7Department of Emergency Medicine, Asahikawa Medical University, Asahikawa, Japan
8Department of Forensic Medicine, Tokai University School of Medicine, Isehara, Japan
9Forensic Medicine Unit, Finnish Institute for Health and Welfare (THL), Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 12.3 MB)
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Language: English
Published: Elsevier, 2023
Publish Date: 2023-10-06


Background: Most platelets are present in peripheral blood, but some are stored in the spleen. Because the tissue environments of peripheral blood vessels and the spleen are quite distinct, the properties of platelets present in each may also differ. However, no studies have addressed this difference. We previously reported that hypothermia activates splenic platelets, but not peripheral blood platelets, whose biological significance remains unknown. In this study, we focused on platelet-derived microvesicles (PDMVs) and analyzed their biological significance connected to intrasplenic platelet activation during hypothermia.

Methods: C57Bl/6 mice were placed in an environment of −20 °C, and their rectal temperature was decreased to 15 °C to model hypothermia. Platelets and skeletal muscle tissue were collected and analyzed for their interactions.

Results: Transcriptomic changes between splenic and peripheral platelets were greater in hypothermic mice than in normal mice. Electron microscopy and real-time RT-PCR analysis revealed that platelets activated in the spleen by hypothermia internalized transcripts, encoding tissue repairing proteins, into PDMVs and released them into the plasma. Plasma microvesicles from hypothermic mice promoted wound healing in the mouse myoblast cell line C2C12. Skeletal muscles in hypothermic mice were damaged but recovered within 24 h after rewarming. However, splenectomy delayed recovery from skeletal muscle injury after the mice were rewarmed.

Conclusions: These results indicate that PDMVs released from activated platelets in the spleen play an important role in the repair of skeletal muscle damaged by hypothermia.

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Series: Thrombosis research
ISSN: 0049-3848
ISSN-E: 1879-2472
ISSN-L: 0049-3848
Volume: 223
Pages: 155 - 167
DOI: 10.1016/j.thromres.2023.01.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was supported by the following grants: Overseas Research Fellowships (grant number 202160207) from the Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research KAKENHI (grant number 21K17328) to KH from JSPS, Bilateral Programs Joint Research Projects/Seminars (grant number JPJSBP120209904) to HT from JSPS, and KI Foundation for Coagulation Research 2022 to KH from the Karolinska Institutet.
Copyright information: © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (