A Study Of Plasma MicroRNA Expression Profiling In Macrovascular Complications Of Type2Diabetes

Objective:To investigate the aberrant expression of plasma microRNA(miRNA) in patients with type2diabetic macrovascular complications, and seek biological markers for early diagnosis,and explore its potential mechanism in the macrovascular complications.Methods:(1)a microRNA PCR array was used to investigate the abnormal expressed plasma miRNAs in patients with diabetic macrovascular complications type2diabetes and healthy controls,3in each group. Then, miRNAs meet the conditions including high expression level, obvious difference and diabetes-related were selected for further study.(2)Four miRNAs (miR-92a,miR-146a,miR-27a and miR-24) were identified to conform the miRNA PCR array data by real-time quantitative PCR (qRT-PCR) in healthy controls, type2diabetes, macrovascular complications,20in each; as well as evaluate the four miRNAs value in the diagnosis of diabetic vascular complications and analyze its relationship with clinical parameters.Result:(1)the result of miRNA chip showed:when compared to type2diabetes, a total of31miRNAs (19upregulated and12downregulated) were differentially expressed in macrovascular complication patients.When compared to healthy control, a total of44miRNAs(18upregulated and26downregulated) were differentially expressed in macrovascular complication patients.When compared to healthy control, a total of25miRNAs(3upregulated and22downregulated) were differentially expressed in diabetes.(2) miR-92a,miR-146a,miR-27a,miR-24were selected for further study.RT-qPCR results showed that compared to healthy controls, miR-92a, miR-27a, miR-146a, miR-24were down-regulated in diabetes and macrovascular complications. miR-92a were all significantly changed(p<0.05) when compared any two groups. miR-27a were significantly down-regulated(P<0.05) in macrovascular complications compared to healthy controls and diabetes. miR-146a were significantly down-regulated(P<0.05) in macrovascular complications compared to healthy controls. miR-24did not have significant changes when compared any two groups(P>0.05).miR-92a,miR-146a and miR-27a have the best value and accuracy as a whole to diagnosis macrovascular complications. The areas under the receiver operating characteristic (ROC) curve of this three-plasma miRNA signature were1.0(P<0.001)and0.926(P<0.001) for macrovascular complications distinguished from the healthy control and the diabetes respectively. Multiple correlation analysis showed that miR-92a,-27a,-146a,-24were correlated with FBG (fasting plasma glucose), BMI(body mass index), the duration of diabetes, HbAlC and WHR significantly(P<0.05).miR-92a also significantly correlated with triglyceride and high density lipoprotein(P<0.05).Bioinformatics used to analysis the potential roles of these differentially expressed plasma miRNAs in the pathogenesis of vascular complication showed that they possibility play roles in cytokine-cytokine receptor interaction, insulin signaling pathway, fatty acid metabolism and so on.Conclusion:the miRNA chip can be used as an important means of screening biomarkers for diabetic macrovascular complications. miR-92a,miR-146a,miR-27a could be potential attractive biomarkers. And we speculate that these miRNAs may play a functional role in diabetic macrovascular complications through cytokine-cytokine receptor interaction, insulin signaling pathway, fatty acid metabolism and so on.