title: 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.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yan
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Affiliated TCM Hospital, Sichuan Medical University, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mu
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Mao
authors.initials: M
authors.lastname: Luo
authors.affiliation: Drug Discovery Research Center, Luzhou, Sichuan, Sichuan Medical University, People's Republic of China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Ren
authors.affiliation: 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: wuji@missouri.edu.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D000068258:Bevacizumab / Q000494:pharmacology*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006614:Hindlimb; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D012039:Regional Blood Flow; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077214:Becaplermin; D000068258:Bevacizumab
keywords: Angiogenesis; Diabetes; Vascular endothelial growth factor; Vascular remodeling