title: Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of Arginase I (ArgI) on plaque stabilization in unruptured atherosclerotic plaque and explore its mechanism.
  
  
  RESULTS
  The atherosclerotic plaque model was established in New Zealand rabbits by balloon injury of abdominal arteries and a high cholesterol (1%) diet. Arginase I overexpression reduced the content of macrophages and lipids and increased that of smooth muscle cells and collagen in the atherosclerotic plaque, thus contributing to decreased plaque vulnerability. Arginase I overexpression decreased the expression of the inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as inducible nitric oxide synthase (iNOS) in plaques. In vitro, ArgI overexpression or iNOS inhibition abolished the secretion of TNF-α and IL-6 induced by lipopolysaccharide in Raw264.7 cells. However, exogenous l-arginine restored the expression of inflammatory cytokines. Arginase I overexpression inhibited the activity of iNOS without changing its expression. Moreover, ArgI co-localized with iNOS in both Raw264.7 cells and human aortic atherosclerotic plaques. In addition, the IL-10 level was increased in plaque with ArgI overexpression. Finally, ArgI promoted aortic vascular smooth muscle cell proliferation, which was associated with increased production of intracellular polyamines.
  
  
  CONCLUSIONS
  ArgI enhances the stability of atherosclerotic plaque by inhibiting the expression of inflammatory cytokines and stimulating smooth muscle cell proliferation.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong 250012, P.R. China.
authors.forename: Xu-Ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Liu
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Wen-Qian
authors.initials: WQ
authors.lastname: Dong
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000201:enzymology*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C574619:ARG1 protein, human; D001119:Arginase
keywords: Arginase I; Atherosclerotic plaque stability; Inflammation; Proliferation