Journal article
Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
International journal of molecular sciences, Vol.14(8), pp.17017-17028
08/19/2013
DOI: 10.3390/ijms140817017
PMCID: PMC3759949
PMID: 23965970
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 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.
Details
- Title: Subtitle
- Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis
- Creators
- Kara Kinkade - University of IowaJennifer Streeter - University of IowaFrancis J. Miller - University of Iowa
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.14(8), pp.17017-17028
- Publisher
- MDPI AG
- DOI
- 10.3390/ijms140817017
- PMID
- 23965970
- PMCID
- PMC3759949
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Number of pages
- 12
- Grant note
- I01BX001729 / Veterans Affairs; US Department of Veterans Affairs PRE12060526 / American Heart Association Predoctoral Fellowship; American Heart Association R01HL081750 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 1BX001729 / Office of Research and Development, Department of Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Date published
- 08/19/2013
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984618515602771
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