title: Early adventitial activation characterized by NADPH oxidase expression and neovascularization in an aortic transplantation model.
abstract: Increasing evidence has suggested that arterial adventitia may contribute to pathological vessel remodeling by producing reactive oxygen species and promoting neovascularization. However, these processes have not been studied yet in transplantation-induced vascular pathologies. We characterized the dynamic changes in NADPH oxidase expression and adventitial angiogenic response in a model of allograft aortic transplantation. The thoracic aorta from Fischer 344 rats were transplanted into the abdominal aorta of Lewis rats. Graft specimens were collected on days 0.5, 3, 7, and 14 for morphometry, immunohistochemistry, immunofluorescence staining, and quantitative PCR tests. Following transplantation, adventitial thickening was found as early as day 3, while neointima was observed from day 7. As compared to normal adventitial tissue, the expression levels of NADPH oxidase subunits gp91phox and p47phox in graft adventitia were elevated from day 3 and further increased up to day 14. Immunohistochemistry staining showed that infiltrating macrophages appeared to be a major source of NADPH oxidase expression. Increases in NADPH oxidase expression were also detected in fibroblasts isolated from the graft adventitia. Gene silencing of p47phox significantly suppressed proliferation and migration of the graft fibroblast cells. We also showed that adventitial thickening was accompanied by increased adventitial neovascularization; at day 14, there was a positive correlation between the density of adventitial microvessels and the neointimal thickness. Transplantation injury induces NADPH oxidase expression and neovascularization in the adventitia, raising the possibility that the activated adventitia may represent a target site for prevention of transplantation-induced transplant vasculopathy.
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: sunmyhappy@163.com.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China; Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: jijian1981@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: 761746150@qq.com.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: 18560081165@163.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: 156085820@qq.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Stomatology, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: zhuzhu292929@163.com.
authors.forename: Siqin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: huweicheng@sdu.edu.cn.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: wangmaq@sdu.edu.cn.
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Pathophysiology, School of Medicine, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: fjiang@sdu.edu.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000637:transplantation*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: Adventitia; Fibroblast; NADPH oxidase; Neovascularization; Transplant vasculopathy