AKT1 and ischemia: In PAD models, Mallat et al. reported endogenous IL-18 is an inhibitor of ischemia-induced neovascularization in the mouse hind limb [45] When treated in vivo with IL-18BP, enhanced neovascularization in the ischemic hind limb was seen by promoting VEGF production and by activating the protein kinase B (Akt) pathway [45].