Circulating endothelial microvesicles and their carried miR-125a 5p:potential biomarkers for ischaemic stroke

Background Endothelial microvesicles(EMVs)are closely associated with the status of endothelial cells(ECs).Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a 5p.However,whether circulating EMVs and their carried miR-125a 5p can be used as biomarkers in ischaemic stroke(IS)are remain unknown.Methods We recruited 72 subjects with IS,60 subjects with high stroke risk and 56 age-matched controls.The circulating EMVs and their carried miR-125a 5p(EMV-miR 125a 5p)levels were detected.We used microRNA(miR)array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls.Transient middle cerebral artery occlusion(tMCAO)was used to establish IS mouse model.Results EMVs level was obviously elevated in IS patients,with the highest level in acute stage,and was positively related to carotid plaque,carotid intima-media thickness(IMT),National Institutes of Health Stroke Scale(NIHSS),infarct volume.On the contrary,we observed that EMV-miR 125a 5p level was obviously reduced in IS,with the lowest level in acute stage,and was negatively correlated with carotid plaque,IMT,NIHSS scores,infarct volume.EMVs and EMV-miR 125a 5p levels were closely related with large artery atherosclerosis subgroup.Importantly,EMVs and EMV-miR 125a 5p levels could serve as independent risk factors,and receiver operating characteristic curve achieved an area under curve(AUC)of 0.720 and 0.832 for IS,respectively,and elevated to 0.881 after their combination.In IS mouse model,control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score,while increase the cerebral blood flow of IS mice compared with vehicle group,while IS EMVs or oxygen and glucose deprivation(OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury.In addition,we observed that OGD EMVmiR-125a 5p could partially ameliorate the OGD EMVs induced brain injury after IS.Conclusions These findings demonstrate that circulating EMVs and EMV-miR 125a 5p are closely related with the occurrence,progress,subtypes and severity of IS,and they can serve as innovative biomarkers and therapeutic targets for IS,especially when they are combined.