title: Adventitial gene transfer of catalase attenuates angiotensin II-induced vascular remodeling.
abstract: Vascular adventitia and adventitia‑derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti‑oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII‑induced vascular remodeling in vivo. Adenoviruses co‑expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague‑Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen‑activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII‑induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII‑induced media hypertrophy compared with that of the control virus (P<0.05). In addition, catalase transfection significantly attenuated AngII‑induced ROS generation, macrophage infiltration, collagen deposition and adventitial α‑smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII‑induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII‑induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Cun-Fei
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, Zhoushan People's Hospital, Zhoushan, Zhejiang 316000, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: Shanghai Key Laboratory of Vascular Biology at Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Hai-Ya
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
authors.forename: Ning-Yuan
authors.initials: NY
authors.lastname: Fang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D063194:Adventitia / Q000187:drug effects* / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D008264:Macrophages / Q000473:pathology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014161:Transduction, Genetic; D014162:Transfection; D066253:Vascular Remodeling / Q000187:drug effects* / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D003094:Collagen; D002374:Catalase; D048051:p38 Mitogen-Activated Protein Kinases