In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 295, No. 4 ( 2008-10), p. H1403-H1413
Abstract:
Epidemiological and clinical studies provide compelling support for a causal relationship between Helicobacter pylori infection and endothelial dysfunction, leading to vascular diseases. However, clear biochemical evidence for this association is limited. In the present study, we have conducted a comprehensive investigation of endothelial injury in bovine aortic endothelial cells (BAECs) induced by H. pylori-conditioned medium (HPCM) prepared from H. pylori 60190 [vacuolating cytotoxin A (Vac + )]. BAECs were treated with either unconditioned media, HPCM (0–25% vol/vol), or Escherichia coli-conditioned media for 24 h, and cell functions were monitored. Vac + HPCM significantly decreased BAEC proliferation, tube formation, and migration (by up to 44%, 65%, and 28%, respectively). Posttreatment, we also observed sporadic zonnula occludens-1 immunolocalization along the cell-cell border, and increased BAEC permeability to FD40 Dextran, indicating barrier reduction. These effects were blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid (VacA inhibitor) and were not observed with conditioned media prepared from either VacA-deleted H. pylori or E. coli. The cellular mechanism mediating these events was also considered. Vac + HPCM (but not Vac − ) reduced nitric oxide (NO) by 〉 50%, whereas S-nitroso- N-acetylpenicillamine, an NO donor, recovered all Vac + HPCM-dependent effects on cell functions. We further demonstrated that laminar shear stress, an endothelial NO synthase/NO stimulus in vivo, could also recover the Vac + HPCM-induced decreases in BAEC functions. This study shows, for the first time, a significant proatherogenic effect of H. pylori-secreted factors on a range of vascular endothelial dysfunction markers. Specifically, the VacA-dependent reduction in endothelial NO is indicated in these events. The atheroprotective impact of laminar shear stress in this context is also evident.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00240.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477308-9
SSG:
12
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