Xanthine oxidase interaction with vascular endothelial growth factor in human endothelial cell angiogenesis
Kou, Baijun, Ni, Jinsong, Vatish, Manu and Singer, Donald R. J.. (2008) Xanthine oxidase interaction with vascular endothelial growth factor in human endothelial cell angiogenesis. Microcirculation, Volume 15 (Number 3). pp. 251-267. ISSN 1073-9688Full text not available from this repository.
Official URL: http://dx.doi.org/10.1080/1073968070165149
Objectives: Reduced capillary density occurs early in cardiovascular diseases. Oxidant stress, is implicated in endothelial apoptosis. We investigated the effects of xanthine oxidase (XO) on endothelial survival signaling: protein kinase B/Akt, its cross-talk with p38 MAPK and apoptosis pathways, and its effect on vascular tube formation in vascular endothelial growth factor (VEGF)-simulated human umbilical vein cells.
Methods: We studied primary cultured human endothelial cells from the umbilical cord. Reactive oxygen species (ROS) production was detected by dibydroethidium staining, cell-signaling pathways by western blots, cell survival by western blots, and nuclear chromatin and angiogenesis response by MTT proliferation assay and three-dimensional Matrigel cultures.
Results: Exogenous XO increased cellular ROS production and caused superoxide-dependent inhibition of Akt phosphorylation and enhancement of p38 MAPK phosphorylation in a time- and dose-dependent mariner. In contrast, application of the XO inhibitor oxypurinol or allopurinol inhibited VEGF-stimulated Akt phosphorylation, indicating that endogenous XO promotes VEGF-induced endothelial cell (EC) survival signaling. Exogenous XO induced activation of caspase-3 and reduced expression of the anti-apoptosis protein Bcl-2. Exogenous XO also reduced EC viability, proliferation, and vascular tube formation by p38 MAPK-dependent, phospboinositide 3-kinase (P13-K) reversible mechanisms; whereas VEGF promoted EC survival by PT3-K-dependent, p38 MAPK-independent effects.
Conclusions: Exogenous XO activity is an important contributor to endothelial mechanisms for microvascular rarefaction., by modulation of cell survival signaling pathways; however, endogenons XO is necessary for maintaining EC survival.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
R Medicine > RC Internal medicine
|Divisions:||Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School > Translational & Systems Medicine > Reproductive Health
Faculty of Medicine > Warwick Medical School
|Library of Congress Subject Headings (LCSH):||Neovascularization, Oxidative stress, Cellular signal transduction, Phosphorylation, Endothelial cells, Vascular endothelial growth factors, Xanthine|
|Journal or Publication Title:||Microcirculation|
|Publisher:||John Wiley & Sons Ltd.|
|Official Date:||April 2008|
|Number of Pages:||17|
|Page Range:||pp. 251-267|
|Access rights to Published version:||Restricted or Subscription Access|
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