Role of oxidative stress via miR‐199a in vascular dysfunction of thoracic aorta from diabetic rats

Abstract

Diabetes is known to be associated with severe cardiovascular dysfunction and hyperglycemia induces alterations in intracellular signal transduction cascades, including generation of reactive oxygen species. Although exact mechanism of diabetes-induced vascular changes has not been elucidated yet, increased oxidative stress is one of major contributors to these events. Previously, we demonstrated that an antioxidant treatment can ameliorate cardiac and vascular dysfunction in diabetic rats. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have shown that there are close relationship between functional changes and altereation in miRNAs including miR-199a due to duration of diabetes. In that regard, we aimed to investigate the role of miR-199a in oxidative stress-induced vascular dysfunction using an antioxidant, selenium in diabetic rats. Thoracic aorta from diabetic rats showed alteration of multiple miRNAs by array analysis. We further investigated the aorta by using real-time PCR of miRNAs, which are closely related with diabetic cardiomyopathy. PCR analysis of miR-199a demonstrated that there is a downregulation (25% compaered to control) in miR-199a level of endothelium-intact aorta from diabetic rats which is fully prevented with sodium selenate treatment. These results fully coincide with functional data. Taken together, it can be proposed a possible relation between increased oxidative stress, downregulation of miR-199a and endothelial vaascular dysfunction in diabetic rats. (Supported by TUBITAK-SBAG-109S267)