Objective To investigate the role of vascular endothelial growth factor-activating transcriptional factor （VEGF-ATF） on the VEGF signaling pathway in diabetes mellitus. Methods Totally

20 C57BL/6 mice fed with high fat diet was induced into diabetes mellitus. Ten diabetes mellitus mice received a lower limb muscle injection with VEGF-ATF plasmid

and another ten were as control. VEGF-ATF is an engineered transcription factor designed to increase VEGF expression. Three days later

mice were sacrificed and the injected gastrocnemius was used for analysis. VEGF mRNA and protein expressions were examined by real-time PCR and ELISA respectively. VEGF receptor 2 mRNA expression was tested with RT-PCR. Phosphorylated Akt

Akt

endothelial nitric oxide synthase （eNOS）

and phosphorylated eNOS were assessed by western blot. Results At 3 days post-injection

in mice with diabetes mellitus

VEGF gene transfer increased VEGF mRNA copies and VEGF protein expression in injected muscles compared with control; and reinstated the impaired VEGF signaling pathway with increasing the ratios of phosphorylated Akt/Akt and phosphorylated eNOS/eNOS. However

it did not affect the expression of VEGF receptor 2 mRNA. Conclusion Gene transfer with VEGF-ATF is able to reinstate the impaired VEGF downstream pathway

and potentially promote therapeutic angiogenesis in mice with diabetes mellitus.