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.
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Long-term high-fat feeding results in abnormal regulation of VEGF-A expression, with decreased VEGF-A levels in adipose tissue of obese mice and humans.
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From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [83]
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- Authors
- Xiao, L., Yan, K., Yang, Y., Chen, N., Li, Y., Deng, X., Wang, L., Liu, Y., Mu, L., Li, R., Luo, M., Ren, M., & Wu, J.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Wu, Jianbo
- Venue
- Microvascular Research
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 105
- Pages
- 70-76
- ISSN
- 0026-2862 (ISSN-L)
- OpenAlex
- W2251066445
- Cited by
- 20
- References
- 31
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 3 · 2021: 5 · 2019: 3 · 2018: 3 · 2017: 1
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microvascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association Scientist Development (10SDG2570037)
- National Natural Science Foundation of China (81172050)
- Grant of Sichuan Province Science and Technology Agency (2014FZ0104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- bevacizumab, anti-VEGF therapy, VEGF-A, PDGF-BB, vascular normalization, hindlimb ischemia, diabetic peripheral arterial disease, blood flow recovery, pericyte recruitment, vascular leakage, angiogenesis, high-fat diet-induced diabetes, microangiopathy
- MeSH terms
- Bevacizumab, Becaplermin, Animals, Diabetic Angiopathies, Disease Models, Animal, Hindlimb, Ischemia, Male, Mice, Inbred C57BL, Neovascularization, Pathologic, Regional Blood Flow, Time Factors, Signal Transduction, Muscle, Skeletal, Angiogenesis Inhibitors, Proto-Oncogene Proteins c-sis, Vascular Endothelial Growth Factor A, Peripheral Arterial Disease, Diet, High-Fat, Vascular Remodeling
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