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Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.

Publication ,  Journal Article
Kinkade, K; Streeter, J; Miller, FJ
Published in: Int J Mol Sci
August 19, 2013

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.

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Published In

Int J Mol Sci

DOI

EISSN

1422-0067

Publication Date

August 19, 2013

Volume

14

Issue

8

Start / End Page

17017 / 17028

Location

Switzerland

Related Subject Headings

  • Superoxides
  • Respiratory Burst
  • Protein Transport
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Leukocytes
  • Hypercholesterolemia
 

Citation

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Kinkade, K., Streeter, J., & Miller, F. J. (2013). Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis. Int J Mol Sci, 14(8), 17017–17028. https://doi.org/10.3390/ijms140817017
Kinkade, Kara, Jennifer Streeter, and Francis J. Miller. “Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.Int J Mol Sci 14, no. 8 (August 19, 2013): 17017–28. https://doi.org/10.3390/ijms140817017.
Kinkade K, Streeter J, Miller FJ. Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis. Int J Mol Sci. 2013 Aug 19;14(8):17017–28.
Kinkade, Kara, et al. “Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.Int J Mol Sci, vol. 14, no. 8, Aug. 2013, pp. 17017–28. Pubmed, doi:10.3390/ijms140817017.
Kinkade K, Streeter J, Miller FJ. Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis. Int J Mol Sci. 2013 Aug 19;14(8):17017–17028.

Published In

Int J Mol Sci

DOI

EISSN

1422-0067

Publication Date

August 19, 2013

Volume

14

Issue

8

Start / End Page

17017 / 17028

Location

Switzerland

Related Subject Headings

  • Superoxides
  • Respiratory Burst
  • Protein Transport
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Leukocytes
  • Hypercholesterolemia