Case Control Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 16, 2023; 11(2): 342-356
Published online Jan 16, 2023. doi: 10.12998/wjcc.v11.i2.342
Microvesicles with mitochondrial content are increased in patients with sepsis and associated with inflammatory responses
Hai-Jun Zhang, Jin-Yi Li, Chao Wang, Guo-Qiang Zhong
Hai-Jun Zhang, Chao Wang, Guo-Qiang Zhong, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
Hai-Jun Zhang, Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421000, Hunan Province, China
Jin-Yi Li, Department of Cardiology, The Affiliated Hospital of Guilin Medical University, Guilin 541000, Guangxi Zhuang Autonomous Region, China
Author contributions: Zhang HJ participated in the study design, collected the samples, performed the experiments, and drafted the manuscript; Li JY helped to carry out the MV number experiments and analyze the data; Wang C helped to collect the samples and modify the manuscript; Zhong GQ conceived the study, participated in the study design, and helped to modify the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The study design was approved by the Ethics Committee of the First Affiliated Hospital of University of South China(protocol code 2020110323009).
Informed consent statement: Informed consent was obtained from all subjects involved in the study.
Conflict-of-interest statement: All the authors declare no conflict of interest.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Qiang Zhong, PhD, Professor, Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530000, Guangxi Zhuang Autonomous Region, China. gq_zhong620@126.com
Received: November 5, 2022
Peer-review started: November 5, 2022
First decision: November 22, 2022
Revised: December 3, 2022
Accepted: December 23, 2022
Article in press: December 23, 2022
Published online: January 16, 2023
Abstract
BACKGROUND

Endothelial activation plays an important role in sepsis-mediated inflammation, but the triggering factors have not been fully elucidated. Microvesicles carrying mitochondrial content (mitoMVs) have been implicated in several diseases and shown to induce endothelial activation.

AIM

To explore whether mitoMVs constitute a subset of MVs isolated from plasma of patients with sepsis and contribute to endothelial activation.

METHODS

MVs were isolated from human plasma and characterized by confocal microscopy and flow cytometry. Proinflammatory cytokines, including interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, and soluble vascular cell adhesion molecule (sVCAM)-1 were detected by ELISA. Human umbilical vein endothelial cells (HUVECs) were stimulated with the circulating MVs to evaluate their effect on endothelial activation.

RESULTS

MitoMVs were observed in plasma from patients with sepsis. Compared with those in healthy controls, expression of MVs, mitoMVs, proinflammatory cytokines and sVCAM-1 was increased. The number of mitoMVs was positively associated with TNF-α and sVCAM-1. In vitro, compared with MVs isolated from the plasma of healthy controls, MVs isolated from the plasma of patients with sepsis induced expression of OAS2, RSAD2, and CXCL10 in HUVECs. MitoMVs were taken up by HUVECs, and sonication of MVs significantly reduced the uptake of mitoMVs by HUVECs and expression of the above three type I IFN-dependent genes.

CONCLUSION

MitoMVs are increased in the plasma of patients with sepsis, which induces elevated expression of type I IFN-dependent genes. This suggests that circulating mitoMVs activate the type I IFN signalling pathway in endothelial cells and lead to endothelial activation.

Keywords: Sepsis, Microvesicles, Mitochondria, Microvesicles carrying mitochondrial content

Core Tip: Sepsis is a systemic inflammatory response syndrome that can lead to multiple organ dysfunction related to endothelial injury. Increased numbers of circulating microvesicles carrying mitochondrial content (mitoMVs) have been found in patients with systemic lupus erythematosus, which feature inflammation as the pathogenic mechanism. Mitochondrial damage-associated molecular patterns have been shown to induce endothelial activation. Therefore, the presence and function of mitoMVs in sepsis was studied. We found that mitoMVs were increased in plasma of patients with sepsis, and were related to inflammatory markers and induced elevated expression of type-I-IFN-dependent genes in endothelial cells.