Hyperglycemia induced microRNAs in endothelial dysfunction

Hyperglycemia is a hallmark in prediabetes and type 2 diabetes mellitus (T2DM) which increases risk of micro and macrovascular complications such as diabetic retinopathy, diabetic nephropathy (microvascular complications), and peripheral vascular disease, cerebrovascular disease and cardiovascular diseases (macrovascular complications). Endothelial cells are affected in both cases. In this study, we investigated the miRNA expression changes in HUVECs during different glucose treatment (5mM, 10mM, 25mM and 40mM glucose) at various time intervals (6, 12, 24 and 48hrs). The results of miRNA microarray showed there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico prediction showed that the following pathways: Regulation of actin cytoskeleton, PI3K-Akt signaling pathway, Apoptosis, Neurotrophin signaling pathway, and Insulin signaling pathway, were dysregulated during hyperglycemia. Majority of the pathways are related to apoptosis. 10 miRNAs (miR-26a-5p, -26b-5p, 29b-3p, 29c-3p, 125b-1-3p, -130b-3p, - 140-5p, -221-3p, -192-5p, and -320a,) showed increased expression with increasing concentration of glucose treatment. miR-26a-5p, -29b-3p, - 140-5p, -221-3p, and -192-5p are involves in endothelial apoptosis. Our study revealed miRNAs (miR-29b-3p and – 192-5p) with known mRNA targets (BCL2 and MCL1) showed expression pattern inversely correlating with their respective target mRNAs. Therefore these miRNAs could involve in the endothelial dysfunction due to hyperglycemia. HUVECs subjected to 0mM to 40mM glucose treatment at different time intervals (6, 12, 24 and 48hrs)