Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

Figure 3

Pathways involved in diabetes-induced EPCs toxicity and possible strategies to reverse EPCs damage during homing. EPCs homing in the sites of ischemia/damage and differentiating into endothelial cells are here represented. Hyperglycemia, Ox-LDL, and AGEs accumulation reduce EPCs adhesion and differentiation ability in both in vivo and in vitro assays. Benfotiamine, an antioxidant molecule, is able to reverse EPCs dysfunction in homing and differentiation. 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. MMP-9: matrix metalloproteinase-9; ROS: reactive oxygen species; NO: nitric oxide; eNOS: endothelial nitric oxide synthase; SDF-1α: stem-cell-derived factor-1α; CXCR-4: C-X-C chemokine receptor type 4; Kit-L: c-Kit ligand; Ox-LDL: oxidized low-density lipoprotein; MAPK: mitogen-activated protein kinase; AGEs: advanced glycation end-products; RAGE: receptor for AGE; IL-8: interleukin-8; VEGF: vascular endothelial growth factor.