Abstract

Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O2 -) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS-/-) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl2. Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NOx (NO2 and NO3), were significantly increased in CaCl2-treated wild type mice. INOS-/- mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NOx in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NOx levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalAtherosclerosis
Volume202
Issue number1
DOIs
StatePublished - Jan 1 2009

Fingerprint

NADPH Oxidase
Nitric Oxide Synthase Type II
Aneurysm
Reactive Oxygen Species
Abdominal Aortic Aneurysm
Inbred C57BL Mouse
Nitric Oxide
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Superoxides
Water

Keywords

  • Abdominal aortic aneurysms
  • Apocynin
  • Inducible nitric oxide synthase
  • NADPH oxidases
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of reactive oxygen species attenuates aneurysm formation in a murine model. / Xiong, Wanfen; Mactaggart, Jason N; Knispel, Rebecca; Worth, Jennifer; Zhu, Zhen; Li, Yulong; Sun, Yimin; Baxter, Bernard Timothy; Johanning, Jason M.

In: Atherosclerosis, Vol. 202, No. 1, 01.01.2009, p. 128-134.

Research output: Contribution to journalArticle

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abstract = "Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O2 -) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS-/-) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl2. Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NOx (NO2 and NO3), were significantly increased in CaCl2-treated wild type mice. INOS-/- mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NOx in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NOx levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.",
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author = "Wanfen Xiong and Mactaggart, {Jason N} and Rebecca Knispel and Jennifer Worth and Zhen Zhu and Yulong Li and Yimin Sun and Baxter, {Bernard Timothy} and Johanning, {Jason M}",
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T1 - Inhibition of reactive oxygen species attenuates aneurysm formation in a murine model

AU - Xiong, Wanfen

AU - Mactaggart, Jason N

AU - Knispel, Rebecca

AU - Worth, Jennifer

AU - Zhu, Zhen

AU - Li, Yulong

AU - Sun, Yimin

AU - Baxter, Bernard Timothy

AU - Johanning, Jason M

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N2 - Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O2 -) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS-/-) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl2. Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NOx (NO2 and NO3), were significantly increased in CaCl2-treated wild type mice. INOS-/- mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NOx in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NOx levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.

AB - Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O2 -) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS-/-) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl2. Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NOx (NO2 and NO3), were significantly increased in CaCl2-treated wild type mice. INOS-/- mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NOx in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NOx levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.

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