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Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice.


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.

SUBMITTER: Park JG 

PROVIDER: S-EPMC5474748 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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<h4>Rationale</h4>Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress.<h4>Objective</h4>Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported.<h4>Methods and results</h4>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 at  ...[more]

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