Impaired angiogenesis following hind-limb ischemia in diabetes mellitus mice.

Objective: To investigate vascular endothelial growth factor (VEGF) and its signaling pathway spontaneous response in type 2 diabetes mellitus (T2DM) mice to surgery-induced hind-limb ischemia.

Methods: Sixty mice were randomly divided into two groups, one was fed with normal chow as control, and another was fed with high fat diet to induce T2DM. Fourteen weeks later, mice were surgically induced to hind-limb ischemia. Blood flow restoration was monitored with laser Doppler perfusion imaging. Tibialis anterior muscle was collected after 3 days of hind-limb ischemia. VEGF mRNA and protein expressions were analyzed using real-time PCR and ELISA; expressions of VEGF downstream signal molecules and receptors were analyzed using Western blotting and RT-PCR, respectively.

Results: Perfusion recovery 10, 20, 30 days after ischemia was significantly attenuated in T2DM compared with control group (P < 0.05). T2DM impaired VEGF signaling pathway although VEGF levels increased in T2DM group. After ischemia, T2DM group had a comparable increase in VEGF expression compared with control group, but still had an impaired VEGF signaling pathway.

Conclusion: VEGF signaling pathway is abnormal in T2DM mice, although VEGF had a response to the ischemic stimulation.