Deficiency in the antioxidant enzyme glutathione peroxidase-1 (Gpx1) does not increase atherosclerosis in C57BL/J6 mice fed a high fat diet

Judy B. de Haan, Paul K. Witting, Nada Stefanovic, Josefa Pete, Michael Daskalakis, Ismail Kola, Roland Stocker, and Joseph J. Smolich

Oxidative Stress Group, Baker Heart Research Institute, Melbourne, Victoria 3181

Corresponding Author: judy.dehaan{at}baker.edu.au

Objective 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). Methods and Results 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 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 pro-inflammatory marker monocyte chemoattractant protein-1 in control, but not Gpx1-deficient mice. Conclusions A specific deficiency in Gpx1 is not accompanied by an increase in markers of oxidative damage or increased atherosclerosis in a murine model of HFD-induced atherogenesis.

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