MiR-92a contributes to the cardiovascular disease development in diabetes mellitus through NF-κB and downstream inflammatory pathways.

ABSTRACT

OBJECTIVE: To explore the role of microRNA-92a (miR-92a) during the development of cardiovascular disease (CAD) in diabetes mellitus (DM) patients, and to investigate its correlation with NF-κB and downstream inflammatory cytokines in diabetes mellitus-associated cardiovascular disease (DM-CAD). PATIENTS AND METHODS: Expression of miR-92a in DM and DM-CAD patients was estimated by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was used to estimate the capability of miR-92a to discriminate between DM-CAD and DM patients. Nuclear factor-κB (NF-κB) p65 protein expression and serum concentrations of monocyte chemotactic protein-1 (MCP-1), endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were investigated. Correlations between miR-92a and NF-κB p65, inflammatory factors were assessed. Risk analysis based on miR-92a was performed for DM-CAD patients. RESULTS: MiR-92a expression was increased in DM-CAD group compared with both DM and healthy groups (all p<0.05). The expression of miR-92a was associated with FIB and HbA1c of DM-CAD patients. MiR-92a could be used to distinguish DM-CAD patients from DM patients with an area under the ROC curve (AUC) of 0.866. Moreover, miR-92a was demonstrated to be a risk factor for DM-CAD onset. Expression levels of NF-κB p65, ET-1, MCP-1, and ICAM-1 were all elevated in DM-CAD patients and shown positive correlations with miR-92a. CONCLUSIONS: Expression of miR-92a in DM-CAD patients is up-regulated, and serves as a potential marker to predict the CAD in DM patients. MiR-92a may contribute to the development of CAD through activation of NF-κB and downstream inflammatory pathways.