MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

Int J Mol Sci. 2016 Apr 7;17(4):518. doi: 10.3390/ijms17040518.

Abstract

Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

Keywords: apoptosis; diabetes mellitus; endothelial dysfunction; hyperglycemia; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / metabolism
  • Cell Survival
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Gene Expression Profiling
  • Glucose / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Hyperglycemia / genetics*
  • Hyperglycemia / metabolism
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Rats

Substances

  • MicroRNAs
  • Caspases
  • Glucose