Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice

Jong Gil Park, Ji Young Yoo, Se Jin Jeong, Jae Hoon Choi, Mi Ran Lee, Mi Ni Lee, Jeong Hwa Lee, Hyoung Chin Kim, Hanjoong Jo, Dae Yeul Yu, Sang Won Kang, Sue Goo Rhee, Mun Han Lee, Goo Taeg Oh

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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.

Original languageEnglish
Pages (from-to)739-749
Number of pages11
JournalCirculation Research
Volume109
Issue number7
DOIs
StatePublished - 16 Sep 2011

Keywords

  • atherosclerosis
  • ICAM-1
  • inflammation
  • peroxiredoxin 2
  • VCAM-1

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