FIGURE 2.

Biochemical and major pathways underlying endothelial dysregulation in vascular complications of diabetes. Long-term hyperglycemia and hyperlipidemia can cause endothelial cell dysfunction and increase the adhesion of monocytes and platelets. The former can transform into macrophages, while the latter can recruit blood cells, accumulate in blood vessels, and form thrombi. On the one hand, macrophages invade endothelial cells and engulf ox-LDL, turning into foam cells and forming arterial plaques. Macrophages release inflammatory and transcription factors that aggravate the inflammatory response. Excessive glucose and lipid levels will covalently combine to form AGEs, which can bind to their receptors; activate the MAPK and NF-KB pathways, among others; and reduce the production and utilization of NO. Abnormal glucose and lipid metabolism can also affect mitochondrial function, produce excessive ROS, and lead to insufficient energy supply. Epigenetic modifications are also closely related to vascular injury in the vascular complications of T2D, including histone and DNA modifications, and ncRNA regulation.