miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients

Rongzong Ye; Qiuyun Lin; Wenkai Xiao; Lixia Mao; Pengfei Zhang; Lingshan Zhou; Xiaoxia Wu; Nannan Jiang; Xihe Zhang; Yinhua Zhang; Daqing Ma; Jiahao Huang; Xiaoyan Wang; Liehua Deng

doi:10.1038/s41420-023-01328-x

miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients

Cell Death Discov. 2023 Jan 21;9(1):19. doi: 10.1038/s41420-023-01328-x.

Authors

Rongzong Ye^#¹, Qiuyun Lin^#¹, Wenkai Xiao^#¹, Lixia Mao¹, Pengfei Zhang¹, Lingshan Zhou¹, Xiaoxia Wu¹, Nannan Jiang¹, Xihe Zhang^{2

3

4}, Yinhua Zhang^{5

6}, Daqing Ma^{7

8}, Jiahao Huang⁹, Xiaoyan Wang^{10

11

12}, Liehua Deng¹³

Affiliations

¹ Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China.
² Doctoral Scientific Research Center, Lianjiang People's Hospital, Zhanjiang, 524400, China.
³ Affiliated Lianjiang People's Hospital, Guangdong Medical University, Zhanjiang, 524400, China.
⁴ Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023, China.
⁵ Department of Physiology & Biomedical Sciences, Ischemic/hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 03080, Korea.
⁶ University Hospital Research Centre, Yanbian University Hospital, Yanji, Jilin Province, 133000, China.
⁷ Division of Anesthetics, Pain, Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
⁸ Chelsea and Westminster, Hospital, London, UK.
⁹ Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China. jhuangaf@connect.ust.hk.
¹⁰ Doctoral Scientific Research Center, Lianjiang People's Hospital, Zhanjiang, 524400, China. cc11wxy@126.com.
¹¹ Affiliated Lianjiang People's Hospital, Guangdong Medical University, Zhanjiang, 524400, China. cc11wxy@126.com.
¹² Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023, China. cc11wxy@126.com.
¹³ Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China. glinson@126.com.

^# Contributed equally.

Abstract

Introduction: Early diagnosis and potential therapeutic targets of sepsis-induced cardiomyopathy (SIC) remain challenges clinically. Circulating extracellular vesicles from immune cells carrying crucial injurious mediators, including miRNAs in sepsis. However, the impacts of neutrophil-derived extracellular vesicles and their miRNAs in the SIC development are unknown.

Objectives: The present study focused on the in-depth miRNA expression profiles of neutrophil-derived extracellular vesicles and explored the potential molecular biomarkers during the process of SIC.

Methods: Neutrophil-derived extracellular vesicles were isolated from the blood samples in three sepsis patients with or without cardiomyopathy on day 1 and day 3 after ICU admission in comparison with three healthy controls. miRNAs were determined by RNA sequencing. The closely related differentially expressed miRNAs with SIC were further validated through qRT-PCR in the other cohorts of sepsis patients with (30 patients) or without cardiomyopathy (20 patients) and the association between miRNAs and the occurrence or disease severity of septic cardiomyopathy were stratified with logistic regression analysis.

Results: Sixty-eight miRNAs from neutrophil-derived extracellular vesicles were changed significantly between healthy controls and without septic cardiomyopathy patients (61 miRNAs upregulated and seven downregulated). Thirty-eight miRNAs were differentially expressed in the septic cardiomyopathy patients. 27 common differentially expressed miRNAs were found in both groups with similar kinetics (23 miRNAs upregulated and four downregulated). The enriched cellular signaling pathway mediated by miRNAs from sepsis to septic cardiomyopathy was the HIF-1 signaling system modulated septic inflammation. Using multivariate logistic regression analysis, miR-150-5p coupled with NT-pro BNP, LVEF, and SOFA score (AUC = 0.941) were found to be the independent predictors of septic cardiomyopathy.

Conclusion: miRNAs derived from neutrophil-derived extracellular vesicles play an important role in septic disease severity development towards cardiomyopathy. miR-150-5p may be a predictor of sepsis severity development but warrants further study.