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Updated: Jun 5, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
MiRNAs and Neutrophil-Related Membrane Proteins from Plasma-Derived Extracellular Vesicles for Early Prediction of
Rongzong Ye1, Yating Wei1, Jingwen Li2
1Department of Emergency Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People's Republic of China.
Purpose:
The pathogenesis of sepsis-induced organ dysfunction remains elusive, and the mortality remains alarmingly high. We sought to investigate the profile of extracellular vesicles (EVs)-mediated communication between plasma and polymorphonuclear neutrophils (PMNs) in sepsis, and to elucidate whether miRNAs and PMN-related membrane proteins from plasma-derived EVs (plasma-EVs) are associated with sepsis-induced organ dysfunction and prognosis.
Methods:
PMN-derived EVs (PMN-EVs) were isolated from the blood samples of healthy controls (N=3) and patients with septic shock (N=3) after ICU admission. We performed miRNA sequencing of the isolated EVs, followed by bioinformatic analysis. A miRNA model for comparing PMN-EVs and plasma-EVs was successfully established in the training cohort. Furthermore, miRNAs and PMN-related membrane proteins from the plasma-EV model were confirmed in the validation cohort. A logistic regression model, receiver operating characteristic (ROC) curves, and Kaplan-Meier analyses were performed to evaluate the efficiency of diagnostic and/or prognostic performance. Further, in vivo and in vitro experiments were conducted to explore the involvement of plasma-EVs in PMNs autophagy.
Results:
Fifty-five miRNAs from PMN-EVs differed significantly between the healthy controls and patients with septic shock. Furthermore, the plasma-EV model (six miRNAs and eight PMN-related membrane proteins) was confirmed in the validation cohort, demonstrating that miR-34a-5p, miR-503-5p, miR-4772-3p, ITGAM, MPO, and MMP9 serve as sepsis biomarkers for distinguishing lung, liver, and kidney dysfunction. Kaplan-Meier survival analysis showed that miR-34a-5p, miR-4772-3p, ITGAM, and MMP9 were potential prognostic predictors. Finally, we found that plasma-EVs from sepsis patients exert an inhibitory effect on PMNs autophagy, which can be reversed by EV inhibitors such as GW4869 and enoxaparin.
Conclusion:
These findings suggest that miRNAs and PMN-related membrane proteins from plasma-EVs could be valuable diagnostic tools for identifying sepsis-induced organ dysfunction and predicting prognosis, enabling proactive management of sepsis by physicians and improving the prognosis of sepsis patients.
