Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

Figure 2

Pathways involved in diabetes-induced EPCs toxicity and possible strategies to reverse EPCs damage during trafficking in the peripheral blood. EPCs trafficking in the peripheral blood are here represented. Hyperglycemia, Ox-LDL, and AGEs accumulation induce an impaired migration ability and reduced cell counts by either increased senescence or increased apoptosis of EPCs in both in vivo and in vitro assays. Statins, Adiponectin, CoPP, and MAPK inhibitors are able to reverse diabetes-mediated damage on circulating EPCs. Diabetes-specific metabolic alterations are in red, linked by red arrows to the pathways they interfere with. Red vertical arrows, next to intracellular or extracellular molecules, indicate that their concentration is diminished or increased in diabetic condition compared to nondiabetic status. Drugs with beneficial effect on EPCs are in green, linked by green arrows to the pathways they interact with. ROS: reactive oxygen species; NO: nitric oxide; eNOS: endothelial nitric oxide synthase; VEGF: vascular endothelial growth factor; Ox-LDL: oxidized low-density lipoprotein; MAPK: mitogen-activated protein kinase; CoPP: cobalt protoporphyrin; AGEs: advanced glycation end-products; RAGE: receptor for AGE; PKC: protein kinase C; IL-8: interleukin-8; COX-2: cyclooxygenase-2.