Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice

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Title
Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice
Author(s)
Jong Gil Park; J Y Yoo; S J Jeong; J H Choi; M R Lee; M N Lee; J H Lee; Hyoung-Chin Kim; H Jo; Dae Yeul Yu; S W Kang; S G Rhee; M H Lee; G T Oh
Bibliographic Citation
Circulation Research, vol. 109, no. 7, pp. 739-749
Publication Year
2011
Abstract
Rationale: Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress. Objective: Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported. Methods and Results: We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H2O2 by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E-deficient (ApoE-/-) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis. Conclusions: Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
Keyword
atherosclerosisICAM-1inflammationperoxiredoxin 2VCAM-1
ISSN
0009-7330
Publisher
Kluwer
DOI
http://dx.doi.org/10.1161/CIRCRESAHA.111.245530
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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