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

Abstract

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.

• Authors: Lamei Xiao, Kai Yan, Yan Yang, Ni Chen, Yongjie Li, Xin Deng, Liqun Wang, Yan Liu, Lin Mu, Rong Li, Mao Luo, Meiping Ren, Jianbo Wu
• Journal: Microvascular research (Microvasc Res) Vol. 105 Pg. 70-6 (May 2016) ISSN: 1095-9319 [Electronic] United States
• PMID: 26808210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Proto-Oncogene Proteins c-sis
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Becaplermin
• Bevacizumab

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Becaplermin
• Bevacizumab (pharmacology)
• Diabetic Angiopathies (drug therapy, etiology, metabolism, physiopathology)
• Diet, High-Fat
• Disease Models, Animal
• Hindlimb
• Ischemia (drug therapy, etiology, metabolism, physiopathology)
• Male
• Mice, Inbred C57BL
• Muscle, Skeletal (blood supply)
• Neovascularization, Pathologic
• Peripheral Arterial Disease (drug therapy, etiology, metabolism, physiopathology)
• Proto-Oncogene Proteins c-sis (metabolism)
• Regional Blood Flow
• Signal Transduction (drug effects)
• Time Factors
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)
• Vascular Remodeling (drug effects)