title: Peroxiredoxin 2 deficiency exacerbates atherosclerosis in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Park
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Yoo
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Lee
authors.forename: Mi-Ni
authors.initials: MN
authors.lastname: Lee
authors.forename: Jeong
authors.initials: J
authors.lastname: Hwa Lee
authors.forename: Hyoung Chin
authors.initials: HC
authors.lastname: Kim
authors.forename: Hanjoong
authors.initials: H
authors.lastname: Jo
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Mun-Han
authors.initials: MH
authors.lastname: Lee
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001393:Azoles / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000201:enzymology; D016026:Bone Marrow Transplantation; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D054833:Isoindoles; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016566:Organoselenium Compounds / Q000494:pharmacology; D054464:Peroxiredoxins / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001393:Azoles; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054833:Isoindoles; D016566:Organoselenium Compounds; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C042986:ebselen; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse