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Microvasc Res. 2016 May;105:70-6. doi: 10.1016/j.mvr.2016.01.005. Epub 2016 Jan 22.

Anti-vascular endothelial growth factor treatment induces blood flow recovery through vascular remodeling in high-fat diet induced diabetic mice.

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Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
Affiliated TCM Hospital, Sichuan Medical University, People's Republic of China.
Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China; Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address:


Diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. The presence of vascular endothelial growth factor (VEGF) can block PDGF-BB dependent regulation of neovascularization and vessel normalization. We tested the hypothesis that the inhibition of VEGF improves blood flow in a mouse hindlimb ischemia model produced by femoral artery ligation. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on blood perfusion and angiogenesis after hindlimb ischemia. We showed that bevacizumab induces functional blood flow in high fat chow (HFC)-fed diabetic mice. Treatment with bevacizumab increased the expression of platelet derived growth factor-BB (PDGF-BB) in ischemic muscle, and led to vascular normalization. It also blocked vascular leakage by improving the recruitment of pericytes associated with nascent blood vessels, but it did not affect capillary formation. Furthermore, treatment with an anti-PDGF drug significantly inhibited blood flow perfusion in diabetic mice treated with bevacizumab. These results indicate that bevacizumab improves blood flow recovery through the induction of PDGF-BB in a diabetic mouse hindlimb ischemia model, and that vessel normalization may represent a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.


Angiogenesis; Diabetes; Vascular endothelial growth factor; Vascular remodeling

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