title: Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet.
abstract: Oxidative stress is thought to contribute to the initiation and progression of atherosclerosis. As glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that detoxifies lipid hydroperoxides, we tested the impact of Gpx1 deficiency on atherosclerotic processes and antioxidant enzyme expression in mice fed a high-fat diet (HFD). After 12 weeks of HFD, atherosclerotic lesions at the aortic sinus were of similar size in control and Gpx1-deficient mice. However, after 20 weeks of HFD, lesion size increased further in control but not in Gpx1-deficient mice, even though plasma and aortic wall markers of oxidative damage did not differ between groups. In control mice, the expression of Gpx1 increased and that of Gpx3 decreased at the aortic sinus after 20 weeks of HFD, with no change in the expression of Gpx2, Gpx4, catalase, peroxiredoxin-6, glutaredoxin-1 and -2, or thioredoxin-1 and -2. By comparison, in Gpx1-deficient mice, the expression of antioxidant genes was unaltered except for a decrease in glutaredoxin-1 and an increase in glutaredoxin-2. These changes were associated with increased expression of the proinflammatory marker monocyte chemoattractant protein-1 in control mice but not in Gpx1-deficient mice. In summary, a specific deficiency in Gpx1 was not accompanied by an increase in markers of oxidative damage or increased atherosclerosis in a murine model of HFD-induced atherogenesis.
authors.affiliation: Oxidative Stress Group, Baker Heart Research Institute, Melbourne, Australia. judy.dehaan@baker.edu.au
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
authors.forename: Nada
authors.initials: N
authors.lastname: Stefanovic
authors.forename: Josefa
authors.initials: J
authors.lastname: Pete
authors.forename: Michael
authors.initials: M
authors.lastname: Daskalakis
authors.forename: Ismail
authors.initials: I
authors.lastname: Kola
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Smolich
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D054477:Glutaredoxins; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; C516006:Glrx protein, mouse; C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D007527:Isoenzymes; D008055:Lipids; D010088:Oxidoreductases; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse