Figure 3.

Main signaling pathways that mediate visfatin/PBEF/Nampt-induced endothelial cell proliferation and migration. Visfatin/PBEF/Nampt promotes vascular endothelial growth factor (VEGF) synthesis and secretion and up-regulates the expression of the VEGF receptor 2. Visfatin/PBEF/Nampt favors the endothelial production of nitric oxide (NO), a promoter of VEGF release, by activating endothelial nitric oxide synthase (eNOS) via the PI3K/Akt pathway. NO production is further enhanced through the activation of dimethylarginine dimethylaminohydrolase (DDAH), which degrades the eNOS inhibitor asymmetric dimethylarginine (ADMA). Additionally, visfatin/PBEF/Nampt triggers the endothelial production of other pro-angiogenic molecules, such as monocyte chemoatractant protein (MCP)-1 and fibroblast growth factor (FGF)-2. On the other hand, visfatin/PBEF/Nampt enhances the levels and activation of matrix metalloproteinases (MMP)-2/9 while decreasing the levels of tissue inhibitor of metalloproteinases (TIMP)-1/2.