Objective To investigate the expression characteristics and clinical significance of endothelial cell-derived extracellular vesicles(EC-EVs)in the peripheral blood of patients with sep-sis-induced cardiomyopathy(SIC).Methods A total of 143 sepsis patients were enrolled and divid-ed 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 isola-tion 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 regres-sion 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.

Objective: To observe the interventional effects of human amniotic mesenchymal stem cells (hAMSCs) transfected with angiotensin converting enzyme 2 (ACE2) gene on monocrotaline-induced pulmonary arterial hypertension (PAH) in rats． Methods : ① HAMSCs were transfected with lentivirus carrying ACE2 gene，and the expression of ACE2，insulin-like growth factor (IGF-1) ，granulocyte chemoattractant protein-2 ( GCP-2) gene，cell migration and tube formation ability was detected before and after transfection. ② Male，healthy，6-week-old SD rats were randomly divided into normal Control group ( Control group ) ，pulmonary hypertension group ( PAH group) ，human amniotic mesenchymal stem cell treatment group ( hAMSCs group) and ACE2-transfected human amniotic mesenchymal stem cell treatment group ( ACE2-hAMSCs group) ．The mean pulmonary arterial pressure ( mPAP) and right ventricular hypertrophy index (RVHI) were measured 2 weeks after the model was established. The lumen size of pulmonary arterioles and the thickness of vessel wall were observed by HE staining．The mRNA expression levels of GCP-2 ，ACE2 ，α-actin and angiotensin Ⅱ ( Ang Ⅱ ) in lung tissue were determined by QPCR . Results : In vitro cell experiments showed that the cell migration ability and tube formation ability of ACE2- hamscs were higher than those of pure hAMSCs (P＜0. 05) ．Ace2-hamscs up-regulated the mRNA expressions of ACE2 and pro-angiogenic factors IGF-1 and GCP-2 (P＜ 0. 01) ．After 2 weeks of intervention，the mPAP and cardiac RV/ LV + S of the PAH group significantly increased compared with the normal control group (P＜0. 01) ，and the mPAP and cardiac RV/ LV + S of the ACE2-hAMSCs group significantly decreased compared with the PAH and hAMSCs groups (P ＜0. 01 ) ． Compared with PAH group，the mRNA expression level of ACE2 significantly increased in the lung tissue of ACE2-hamscs group． Conclusion ACE2-hAMSCs can significantly reduce the mean pulmonary arterial pressure of monocrotaline (MCT) -induced PAH rat model，and significantly improve pulmonary vascular and right ventricular remodeling．The therapeutic effect of ACE2-hamscs is significant in hAMSCs group. It is considered that ACE2-hAMSCs may not only promote the paracrine effect of hAMSCs，The expression of provascular growth factors GCP2 and IGF-1 can repair the injured pulmonary vascular endothelial cells and reduce the high pressure of pulmonary artery．Moreover，the high expression of ACE2 in hAMSCsis related to the regulation of RAS.