miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients.
miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients.
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DOI：
10.1038/s41420-023-01328-x
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发表时间：
2023-01-21
影响因子：
7
通讯作者：
Deng, Liehua
中科院分区：
文献类型：
--
作者：
Ye, Rongzong;Lin, Qiuyun;Xiao, Wenkai;Mao, Lixia;Zhang, Pengfei;Zhou, Lingshan;Wu, Xiaoxia;Jiang, Nannan;Zhang, Xihe;Zhang, Yinhua;Ma, Daqing;Huang, Jiahao;Wang, Xiaoyan;Deng, Liehua
脓毒症心肌病的早期诊断和潜在的治疗靶点仍是临床上的挑战。来自免疫细胞的循环细胞外囊泡携带关键的有害介质，包括脓毒症中的miRNA。然而，嗜中性粒细胞衍生的细胞外囊泡及其miRNA在SIC发育中的影响尚不清楚。本研究旨在深入研究嗜酸性粒细胞来源的细胞外囊泡的miRNA表达谱，并探索SIC过程中潜在的分子生物标志物。中性粒细胞衍生的细胞外囊泡分离自血液样本中的三个脓毒症患者或没有心肌病的第1天和第3天ICU入院后相比，三个健康对照。通过RNA测序确定miRNA。通过qRT-PCR进一步验证了与SIC密切相关的差异表达miRNA在其他脓毒症患者队列中（30例患者）或无心肌病（20例患者），并采用logistic回归分析对miRNA与脓毒症心肌病的发生或疾病严重程度之间的关联进行分层。在健康对照组和非脓毒性心肌病患者之间，来自嗜中性粒细胞来源的细胞外囊泡的68种miRNA发生了显著变化（61种miRNA上调，7种下调）。38个miRNAs在脓毒症心肌病患者中差异表达。在两组中发现了27种常见的差异表达的miRNAs，具有相似的动力学（23种miRNAs上调，4种下调）。从脓毒症到脓毒症心肌病，由miRNAs介导的细胞信号通路是由HIF-1信号系统调控的脓毒症炎症。使用多变量logistic回归分析，发现miR-150- 5 p与NT-pro BNP、LVEF和SOFA评分（AUC = 0.941）结合是脓毒性心肌病的独立预测因子。来源于嗜中性粒细胞衍生的细胞外囊泡的miRNA在脓毒性疾病向心肌病的严重发展中起重要作用。miR-150- 5 p可能是脓毒症严重程度的预测因子，但需要进一步研究。
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. 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. 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. 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. 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.
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影响因子：
4.5
作者：
Chen HP;Wang XY;Pan XY;Hu WW;Cai ST;Joshi K;Deng LH;Ma D
通讯作者：
Ma D
miR-146a 通过靶向 ErbB4 表达抑制 IRAK1 和 TRAF6 减轻脓毒症引起的心肌功能障碍
影响因子：
--
作者：
An R;Feng J;Xi C;Xu J;Sun L
通讯作者：
Sun L
DOI：
10.1186/s13054-015-1162-8
发表时间：
2015-12-18
期刊：
Critical care (London, England)
影响因子：
--
作者：
Goodwin AJ;Guo C;Cook JA;Wolf B;Halushka PV;Fan H
通讯作者：
Fan H
影响因子：
2.7
作者：
Fernández-Messina L;Gutiérrez-Vázquez C;Rivas-García E;Sánchez-Madrid F;de la Fuente H
通讯作者：
de la Fuente H
影响因子：
3.1
作者：
Fernandes, Constantino Jose, Jr.;Akamine, Nelson;Knobel, Elias
通讯作者：
Knobel, Elias