title: The Role of Vascular Endothelial Growth Factor in Small-airway Remodelling in a Rat Model of Chronic Obstructive Pulmonary Disease.
abstract: Small-airway remodelling is one of the most remarkable pathological features of chronic obstructive pulmonary disease (COPD), in which angiogenesis plays a critical role that contributes to disease progression. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF), as well as its receptors, VEGFR1, VEGFR2, are thought to be the major mediators of pathological angiogenesis, and sunitinib exhibits anti-angiogenesis property through VEGF blockage and has been widely used to treat various cancers. In our study, Sprague-Dawley rats were subjected to lipopolysaccharide (LPS) injection and cigarette smoke (CS) inhalation to induce COPD, following sunitinib administration was conducted. Haematoxylin-eosin, Masson staining and immunostaining analysis were used to evaluate the pathological changes; quantitative real-time PCR and enzyme-linked immunosorbent assay were performed to provide more compelling data on the function of VEGF, VEGFR1, VEGFR2 in angiogenesis. Sunitinib treatment was associated with less angiogenesis in small-airway remodelling with a slightly disordered lung architecture, and lower expression level of VEGF, VEGFR1, VEGFR2. Overall, our results indicate that VEGF is a vital important factor that contributes to the small-airway remodelling in a rat model of COPD through promoting angiogenesis, which mainly depend on the specific binding between VEGF and VEGFR1 and can be effectively attenuated by sunitinib.
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of respiration, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, People's Republic of China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Respiratory physiology Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of respiration, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of respiration, Dongyang Hospital of Traditional Chinese Medicine, Jinhua, 322100, People's Republic of China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
authors.forename: Liting
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Respiratory physiology Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
mesh_terms: D056151:Airway Remodeling; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D007211:Indoles / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D011758:Pyrroles / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D012906:Smoke; D000077210:Sunitinib; D014026:Nicotiana / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D008070:Lipopolysaccharides; D011758:Pyrroles; D012906:Smoke; D042461:Vascular Endothelial Growth Factor A; C000602029:Kdr protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib