Oxidative stress in human abdominal aortic aneurysms: A potential mediator of aneurysmal remodeling

Francis J. Miller, William J. Sharp, Xiang Fang, Larry W. Oberley, Terry D. Oberley, Neal L. Weintraub

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by localized connective tissue degradation and smooth muscle cell (SMC) apoptosis, leading to aortic dilatation and rupture. Reactive oxygen species are abundantly produced during inflammatory processes and can stimulate connective tissue-degrading proteases and apoptosis of SMCs. We hypothesized that reactive oxygen species are locally increased in AAA and lead to enhanced oxidative stress. In aortas from patients undergoing surgical repair, superoxide levels (measured by lucigenin-enhanced chemiluminescence) were 2.5-fold higher in the AAA segments compared with the adjacent nonaneurysmal aortic (NA) segments (6638±2164 versus 2675±1027 relative light units for 5 minutes per millimeter squared, respectively; n=7). Formation of thiobarbituric acid-reactive substances and conjugated dienes, 2 indices of lipid peroxidation, were increased 3-fold in AAA compared with NA segments. Immunostaining for nitrotyrosine was significantly greater in AAA tissue. Dihydroethidium staining indicated that increased superoxide in AAA segments was localized to infiltrating inflammatory cells and to SMCs. Expression of the NADPH oxidase subunits p47phox and p22phox and NAD(P)H oxidase activity were increased in AAA segments compared with NA segments. Thus, oxidative stress is markedly increased in AAA, in part through the activation of NAD(P)H oxidase, and may contribute to the disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)560-565
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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Abdominal Aortic Aneurysm
Oxidative Stress
NADPH Oxidase
Superoxides
Connective Tissue
Reactive Oxygen Species
Apoptosis
Aortic Rupture
Thiobarbituric Acid Reactive Substances
Luminescence
Lipid Peroxidation
Smooth Muscle Myocytes
Aorta
Dilatation
Peptide Hydrolases
Staining and Labeling
Light

Keywords

  • Aneurysm
  • Antioxidants
  • Aortas
  • Free radicals
  • NADPH oxidase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Oxidative stress in human abdominal aortic aneurysms : A potential mediator of aneurysmal remodeling. / Miller, Francis J.; Sharp, William J.; Fang, Xiang; Oberley, Larry W.; Oberley, Terry D.; Weintraub, Neal L.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 22, No. 4, 2002, p. 560-565.

Research output: Contribution to journalArticle

Miller, Francis J. ; Sharp, William J. ; Fang, Xiang ; Oberley, Larry W. ; Oberley, Terry D. ; Weintraub, Neal L. / Oxidative stress in human abdominal aortic aneurysms : A potential mediator of aneurysmal remodeling. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 ; Vol. 22, No. 4. pp. 560-565.
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