Advances in neovascularization after diabetic ischemia

Figure 1 Novel mechanisms of neovascularization. When glucose enters the cell through channels that initiate glycolysis in an aerobic environment, when the anaerobic glycolysis, lactic acid can cause macrophages to convert to a repair phenotype. These macrophages will not produce inflammatory factors such as tumor necrosis factor γ and interleukin 12, which promotes angiogenesis. Lactic acid can activate the nuclear factor kappa-B-C-X-C motif chemokine 8 pathway, promote vascular endothelial growth factor (VEGF) secretion, stabilize hypoxia-inducible factor-1α (HIF-1α), and promote angiogenesis. When hypoxia occurs in the environment, it promotes hexokinase, which promotes glycolysis, and AMPK, which promotes hypoxia-inducible factor-1. It then acts on 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3. AMPK also acts directly on 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, and they jointly promote fructose-2,6-biphosphatase, which acts on phosphofructokinase 1 and promotes glycolysis. Hypoxia also promotes VEGF secretion, and a high concentration of VEGF activates the Notch-DLL4 pathway, directly or indirectly promoting the proliferation of tip cells. VEGF also promotes the growth of stalk cells, and both promote angiogenesis. 1,3BPG: 1,3 diphosphoglycerate; 2-PG: 2-phosphoglycerate; 3-PG: 3-phosphoglycerate; F1,6BP: Fructose 1,6-diphosphate; F2,6BP: Fructose 2,6-diphosphate; F6P: Fructose 6 phosphate; G3P: Glyceraldehyde-3-phosphate; G6P: Glucose 6-phosphate; PEP: Phosphoenolpyruvate; Pyr: Pyruvic acid.