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Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA
Veterans Affairs Medical Center, Iowa City, IA 52242, USA
* Author to whom correspondence should be addressed.
Received: 27 May 2013; in revised form: 26 July 2013 / Accepted: 9 August 2013 / Published: 19 August 2013
Abstract: Of the multiple sources of reactive oxygen species (ROS) in the blood vessel, NADPH oxidases are the primary source. Whereas several studies have implicated NADPH oxidases in the initiation of atherosclerosis, their roles in disease progression are incompletely understood. Our objective was to determine the potential clinical relevance of inhibiting NADPH oxidase in established atherosclerosis. Using a hypercholesteremic murine model of atherosclerosis (ApoE−/−/LDLR−/− (AS) mice on normal chow diet), we first established a time-dependent relationship between superoxide levels and lesion size in AS mice. Next, we identified NADPH oxidase as the primary source of ROS in atherosclerotic lesions. Treatment of aortic segments from AS mice with apocynin, which interferes with NADPH oxidase activation in part by preventing translocation of the subunit p47phox, significantly reduced superoxide levels. Moreover, addition of apocynin to the drinking water of AS mice produced a decrease in lesion size as compared to untreated AS mice, with the effect most pronounced in the thoracoabdominal aorta but absent from the aortic arch. Granulocyte function in AS+apocynin mice was suppressed, confirming efficacy of apocynin treatment. We conclude that apocynin attenuates the progression of atherosclerosis in hypercholesterolemic mice, potentially by its ability to inhibit generation of superoxide by NADPH oxidase.
Keywords: NADPH oxidase; apocynin; atherosclerosis; superoxide
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Kinkade, K.; Streeter, J.; Miller, F.J. Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis. Int. J. Mol. Sci. 2013, 14, 17017-17028.
Kinkade K, Streeter J, Miller FJ. Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis. International Journal of Molecular Sciences. 2013; 14(8):17017-17028.
Kinkade, Kara; Streeter, Jennifer; Miller, Francis J. 2013. "Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis." Int. J. Mol. Sci. 14, no. 8: 17017-17028.