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Figure 2. Vascular inflammation in DKD. The schematic illustrates the signaling pathways and mechanisms leading to vascular inflammation in DKD. Both hemodynamic and metabolic alterations in diabetes contribute to the activation of these pathways. While the nitric oxide pathway may be upregulated in the early phases of DKD and contribute to hyperfiltration, NO levels decrease as the course progresses, partly due to NO quenching by superoxide, leading to peroxynitrite, which stimulates inflammatory cytokines. Similarly, endothelin activation by hemodynamic and metabolic factors leads to endothelial injury and vascular inflammation. Chronic uncontrolled hyperglycemia leads to advanced glycation endproducts, which trigger inflammasome and oxidative stress. Ultimately, all the signaling alterations lead to vascular inflammation, contributing in a major way to renal demise in diabetes. AGEs: Advanced glycation endproducts; RAGE: receptor for AGE; TNF-α: tumor necrosis factor-alpha; IL: interleukin; NLRP3: NOD-like receptor family pyrin domain-containing 3; ROS: reactive oxygen species; NO: nitric oxide.