Hyperglycemia initiates N-cadherin rearrangement and diabetic monocytes promote inflammatory responses in human microvascular endothelial cells

Abstract The prevalence of diabetes around the world is increasing, and the complications of diabetes are becoming worse so that the global burden of diabetes-related complications is rising. The purpose of this study was to simulate the physiological condition of diabetes in the human body by culturing human microvascular endothelial cell 1 (HMEC-1) cells in Dulbecco’s modified Eagle’s medium (DMEM) containing 5.5mM glucose, 25mM glucose, and 50mM glucose. The cell viability of HMEC-1 cells at the indicated glucose concentrations was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The specific epithelial cell junction N-cadherin was measured by immunofluorescence. Furthermore, monocytic initiation of inflammatory reactions was studied by using Western blotting and enzyme-linked immunosorbent assay. Based on our results, hyperglycemia treatment influenced the distribution of N-cadherin-containing structures in HMEC-1 cells, whereas the change of the inflammatory profiles in HMEC-1 cells was affected after their coculture with the supernatant of diabetic THP-1 monocytes. In this study, we conclude that the removal of endothelial N-cadherin caused by hyperglycemia (at the 25mM glucose and 50mM glucose concentrations) may lead to endothelial dysfunction and subsequently endothelial cell death in the late stage of diabetes. Furthermore, the loss of intercellular adhesion molecule 1 and the upregulation of interleukin (IL)-1, IL-6, and tumor necrosis factor alpha mediated by diabetic monocytes showed altered interaction between the vascular endothelium and blood cells in the diabetic microenvironment.