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Cited by 461

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress

McNally, J. Scott, Davis, Michael E., Giddens, Don P., Saha, Aniket, Hwang, Jinah, Dikalov, Sergey, Jo, Hanjoong, Harrison, David G.·2003·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00515.2003
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Abstract

Oscillatory shear stress occurs at sites of the circulation that are vulnerable to atherosclerosis. Because oxidative stress contributes to atherosclerosis, we sought to determine whether oscillatory shear stress increases endothelial production of reactive oxygen species and to define the enzymes responsible for this phenomenon. Bovine aortic endothelial cells were exposed to static, laminar (15 dyn/cm 2), and oscillatory shear stress (±15 dyn/cm 2). Oscillatory shear increased superoxide ([Formula: see text]) production by more than threefold over static and laminar conditions as detected using electron spin resonance (ESR). This increase in [Formula: see text] was inhibited by oxypurinol and culture of endothelial cells with tungsten but not by inhibitors of other enzymatic sources. Oxypurinol also prevented H 2 O 2 production in response to oscillatory shear stress as measured by dichlorofluorescin diacetate and Amplex Red fluorescence. Xanthine-dependent [Formula: see text] production was increased in homogenates of endothelial cells exposed to oscillatory shear stress. This was associated with decreased xanthine dehydrogenase (XDH) protein levels and enzymatic activity resulting in an elevated ratio of xanthine oxidase (XO) to XDH. We also studied endothelial cells lacking the p47 phox subunit of the NAD(P)H oxidase. These cells exhibited dramatically depressed [Formula: see text] production and had minimal XO protein and activity. Transfection of these cells with p47 phox restored XO protein levels. Finally, in bovine aortic endothelial cells, prolonged inhibition of the NAD(P)H oxidase with apocynin decreased XO protein levels and prevented endothelial cell stimulation of [Formula: see text] production in response to oscillatory shear stress. These data suggest that the NAD(P)H oxidase maintains endothelial cell XO levels and that XO is responsible for increased reactive oxygen species production in response to oscillatory shear stress.

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Metadata

Authors
McNally, J. S., Davis, M. E., Giddens, D. P., Saha, A., Hwang, J., Dikalov, S., Jo, H., & Harrison, D. G.
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2003-12
Volume
285
Issue
6
Pages
H2290-H2297
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.00515.2003
OpenAlex
W2170551438
Cited by
461
References
2
FWCI
14.29
Type
journal article
Language
en
Open access
closed

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