Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

Figure 1

Pathways involved in diabetes-induced EPCs toxicity and possible strategies to reverse EPCs damage during bone marrow mobilization. EPCs recruited from bone marrow are here represented. Hyperglycemia alters CXCR-4/SDF-1α pathway, reduces VEGF levels, increases eNOS-mediated production of ROS and a reduction in cleaving enzymes activity. ACE inhibitors and GM-CSF administration improve bone marrow ability to shed EPCs in the periphery. 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; GLO-1: glyoxalase-1; ROS: reactive oxygen species; NO: nitric oxide; eNOS: endothelial nitric oxide synthase; HIF1-α: hypoxia inducible factor 1-α; SDF-1α: stem cell-derived factor-1α; CXCR-4: C-X-C chemokine receptor type 4; VEGF: vascular endothelial growth factor; Kit-L: c-Kit ligand.