Expression and significance of endothelial cell-derived extracellular vesicles in peripheral blood of patients with sepsis-induced cardiomyopathy

Objective To investigate the expression characteristics and clinical significance of endothelial cell-derived extracellular vesicles (EC-EVs) in the peripheral blood of patients with sepsis-induced cardiomyopathy (SIC).

Methods A total of 143 sepsis patients were enrolled and divided into cardiomyopathy group (n=72) and non-cardiomyopathy group (n=71) based on occurrence of SIC. Peripheral blood samples were collected from patients in both groups upon admission for isolation and identification of EC-EVs. The number of EC-EVs, apoptosis, and the activity and expression levels of caspase-1 in EC-EVs were compared between the two groups. Spearman correlation analysis was used to assess the correlations of the number of EC-EVs, caspase-1 activity, and N-terminal pro-brain natriuretic peptide (NT-proBNP) with cardiac troponin Ⅰ (cTnⅠ). Multivariable Logistic regression analysis was conducted to explore the factors influencing the occurrence of SIC in sepsis patients. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of the number of EC-EVs and caspase-1 activity for SIC.

Results EC-EVs with a diameter of approximately 100 nm, intact membrane structure, and expression of extracellular vesicles (EVs) marker molecules (CD9, CD63, CD81) were successfully isolated from samples in both groups. The cardiomyopathy group had significantly higher numbers of EC-EVs in peripheral blood, EC-EV apoptosis levels, caspase-1 activity, and protein expression levels compared to the non-cardiomyopathy group(P < 0.05). Spearman correlation analysis revealed positive correlations between the number of EC-EVs and NT-proBNP (r=0.603, 0.685, P < 0.001), and between caspase-1 activity and cTnI (r=0.474, 0.711, P < 0.001). Multivariable Logistic regression analysis showed that the number of EC-EVs, caspase-1 activity, NT-proBNP levels, and cTnI levels were all independent influencing factors for the occurrence of SIC in sepsis patients (P < 0.05). The ROC curves indicated that the areas under the curve for predicting SIC based on the number of EC-EVs and caspase-1 activity in peripheral blood were 0.721 and 0.858, respectively.

Conclusion The number of EC-EVs and caspase-1 activity in EC-EVs in the peripheral blood of SIC patients are significantly increased, and are closely related to cardiac function and myocardial injury in sepsis patients. Thus, they have the potential to become biomarkers for predicting SIC.