Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice
- 주제(키워드) atherosclerosis , ICAM-1 , inflammation , peroxiredoxin 2 , VCAM-1
- 등재 SCIE, SCOPUS
- 발행기관 Lippincott Williams & Wilkins Ltd.
- 발행년도 2011
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000092690
- 본문언어 영어
- Published As http://dx.doi.org/10.1161/CIRCRESAHA.111.245530
초록/요약
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. © 2011 American Heart Association, Inc.
more