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Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis

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 deter...

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Detalles Bibliográficos
Autores principales: Kinkade, Kara, Streeter, Jennifer, Miller, Francis J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759949/
https://www.ncbi.nlm.nih.gov/pubmed/23965970
http://dx.doi.org/10.3390/ijms140817017
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author Kinkade, Kara
Streeter, Jennifer
Miller, Francis J.
author_facet Kinkade, Kara
Streeter, Jennifer
Miller, Francis J.
author_sort Kinkade, Kara
collection PubMed
description 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 p47(phox), 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.
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spelling pubmed-37599492013-09-03 Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis Kinkade, Kara Streeter, Jennifer Miller, Francis J. Int J Mol Sci Article 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 p47(phox), 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. MDPI 2013-08-19 /pmc/articles/PMC3759949/ /pubmed/23965970 http://dx.doi.org/10.3390/ijms140817017 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Kinkade, Kara
Streeter, Jennifer
Miller, Francis J.
Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title_full Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title_fullStr Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title_full_unstemmed Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title_short Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
title_sort inhibition of nadph oxidase by apocynin attenuates progression of atherosclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759949/
https://www.ncbi.nlm.nih.gov/pubmed/23965970
http://dx.doi.org/10.3390/ijms140817017
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