[Therapeutic angiogenesis for diabetes mellitus related ischemic disease]

The complications of diabetes mellitus have a significant impact on patient survival and quality of life with respect to ischemic disease. Therapeutic gene therapy was performed for peripheral artery disease (PAD) using vascular endothelial growth factor (VEGF), but VEGF gene therapy in phase III clinical trial for PAD did not succeed. Although hepatocyte growth factor (HGF) is also a potent angiogenic growth factor in animal models of ischemia, their characteristics are not the same in clinical trials. In this background, we demonstrated that HGF, but not VEGF, attenuated angiotensin II-induced senescence of endothelial progenitor cells through a reduction of oxidative stress by inhibition of the phosphatidylinositol-3,4,5-triphosphate/Akt pathway. Therapeutic gene therapy still may improve patients with the complications of diabetes mellitus.