Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing

Figure 3

Signaling mechanisms leading to endothelial dysfunction under diabetes. Diabetes-mediated hyperglycemia leads to multiple-signal pathway dysfunction within vascular endothelial cells. Primary insults include mitochondrial dysfunction, defective PI3 kinase signaling, decreased NO production, increased oxidative stress, and differential PKC isoform activation. Key words: pARP: poly (ADP-ribose) polymerase; AGE: advance glycation end products; DAG: diacylglycerol; NF-κB: nuclear factor kappa-B; PKC: protein kinase C; iNOS: inducible nitric oxide synthase; NADH: nicotinamide adenine dinucleotide; NO: nitric oxide; RAGE: receptor for advanced glycation endproducts; O₂^•: superoxide anion; ONOO⁻: peroxynitrite; PI3K: phosphatidylinositol 3-kinases; AKT: protein kinase B; eNOS: endothelial nitric oxide synthase; GTPCH: GTP cyclohydrolase; BH4: tetrahydrobiopterin; BH2: dihydrobiopterin.