Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Figure 2

The detrimental effect of hyperglycemia on endothelial progenitor cells (EPCs) number and function. High level of glucose stimulates ROS production through activation of NAPDH oxidase. Increased reactive oxygen species (ROS) production triggers advanced glycated end products (AGEs) formation. AGE in turn further increases ROS production and, in the meantime, promotes nuclear factor-kappa B (NF-κB) transcription. NF-κB is crucially involved in inflammation via transcriptional activation of its target genes such as IL-1β and TNF-α. In parallel, NF-κB also activates p53 to accelerate cell senescence and iNOS that further potentiates ROS production. Except mitochondrial diabetic retinopathy ion damage, hyperglycemia induces endoplasmic reticulum (ER) stress and excessive autophagy to further facilitate EPCs death. Apart from that, hyperglycemia inhibits Akt phosphorylation and subsequently eNOS activation. It also activates p38MAPK pathway to promote cell death and senescence. Ultimately, EPCs are triggered to undergo apoptosis and become dysfunctional.