At the cellular and molecular level, RAGE signal transduction leads to (i) activation of NADPH oxidase, further causing mitochondrial DNA and protein damage [36]; (ii) activation of transcription factor nuclear factor-κB (NF-κB) which plays a fundamental role in the initiation and progression of inflammation through upregulation of cytokines, growth factors and RAGEs itself [37]; and (iii) the activation of mitogen-activated protein kinase leading to endothelial dysfunction, thereby illustrating the complex pathogenesis of diabetic vascular complications [38]. Here, WNK2 is linked to endothelial dysfunction.