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Peroxiredoxin 2 Deficiency Exacerbates Atherosclerosis in Apolipoprotein E-Deficient Mice

Title
Peroxiredoxin 2 Deficiency Exacerbates Atherosclerosis in Apolipoprotein E-Deficient Mice
Author
최재훈
Keywords
peroxiredoxin 2; atherosclerosis; inflammation
Issue Date
2011-09
Publisher
LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
Citation
CIRCULATION RESEARCH, Vol.109, No.7 [2011], p739-U80
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 H(2)O(2) 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. (Circ Res. 2011; 109: 739-749.)
URI
http://circres.ahajournals.org/content/109/7/739
ISSN
0009-7330
DOI
10.1161/CIRCRESAHA.111.245530
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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