title: Overexpression of peroxiredoxin 4 attenuates atherosclerosis in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear.
  
  
  RESULTS
  To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4(+/+)/apoE(-/-)). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE(-/-) mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4(+/+)/apoE(-/-) mice than in apoE(-/-) mice. Bone marrow transplantation from hPRDX4(+/+) donors to apoE(-/-) mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression.
  
  
  METHODS
  In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE(-/-) mice fed a high-cholesterol diet.
  
  
  CONCLUSIONS
  These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques.
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Shohei
authors.initials: S
authors.lastname: Shimajiri
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Murata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Tasaki
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nabeshima
authors.forename: Teruo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins