Oxidative stress in human abdominal aortic aneurysms: a potential mediator of aneurysmal remodeling.
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 p47(phox) and p22(phox) 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.
Miller
Francis J
FJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA. francis-miller@uiowa.edu
Sharp
William J
WJ
Fang
Xiang
X
Oberley
Larry W
LW
Oberley
Terry D
TD
Weintraub
Neal L
NL
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D009249:NADP; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases