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It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC. On the other hand, transfection of an miR-135a inhibitor reversed the activated interaction between monocytes and db/db VSMC. The pro-inflammatory responses could also be enhanced by using siRNAs to silence the FOXO1 gene in WT VSMC, suggesting a negative regulatory role of FOXO1. FOXO1 siRNAs and miR-135a mimics could both enhance the transcriptional activity of COX-2 promoter. Using chromatin immunoprecipitation, we found that in db/db VSMC, the occupancy in promoter regions of inflammatory genes by FOXO1 was reduced.miR-135a increased the inflammatory responses of VSMC involved in complications of vascular diseases by downregulating the expression of FOXO1.

MiR-135a Promotes Inflammatory Responses of Vascular Smooth Muscle Cells From db/db Mice via Downregulation of FOXO1