Overexpression Of Serum Exosomal MiR-628 Induces Cerebral Aneurysm Development In Mice

Purpose:The rupture of intracranial aneurysms can cause subarachnoid hemorrhage,which has a high mortality and morbidity.Therefore,to find the early diagnostic methods of intracranial aneurysms is very necessary.There are present researches using the wall of cerebral aneurysm as object to study the gene expression profile of cerebral aneurysm or the change of mi RNA.This research is based on the previous clinical trials showing that exosomal mi R-628 in blood circulation of patients with intracranial aneurysms raises,and aims to study exosomal mi R-628 in blood circulation induces the formation of cerebral aneurysms by the animal experiment,and judge whether exosomal mi R-628 has the potential of being a biomarker to detect cerebral aneurysms.Methods: 30 male C57BL/6 mice were equally and randomly divided into three groups: normal group,hypertension group,hypertension + mir-628 agomir group.The normal group did not do any treatment as the control group.The hypertension group was established with the left renal artery narrowing method.The hypertensive group and hypertension + mir-628 agomir group were built hypertensive models,then hypertension + mir-628 agomir group mice were injected with25 nmol mir-628 agomir 4 times.After 4 weeks,all 3 groups of mice had perfusion of the willis circle and pathological immunohistochemical analysis.At last,mir-628 levels were compared in the blood circulation of 154 patients with cerebral aneurysms and 55 normal people.Results: In hypertension + mir-628 agomir group the intracranial vascular was dilatated,the vascular wall smooth muscle cells apoptosis,the internal elastic layer and the waveform protein are destroyed.,and 8(80%)mice were observed to form cerebral aneurysms.The median number of exosomal mir-628 levels in patients with cerebral aneurysm and normal was 53.79 + 107.45 and 0.43 + 1.86 respectively.We define when exosomal mir-628 level with an average2-??CT?4.3 was considered to represent cerebral aneurysms,no aneurysm conversely.This diagnosis method compared the results of DSA and/or MRA,accuracy was 88.04%,sensitivity was 84.4%,specificity of 98.2%,positive predictive value was 99.2%,negative predictive value of 69.2%.Conclusions: The overexpression of mi R-628 may induce the formation of cerebral aneurysms,and it is expected to be a biomarker for early diagnosis of intracranial aneurysms.