Fabienne Baffert
Effects of prolonged exposure to hypoxia on morphological changes of endothelial cells plated on fibrin gel
Published on 1 March 2001
Body text 1
-Thesis presented March 01, 2001
Abstract:
Angiogenesis, the formation of new capillaries is observed in tissues subjected to hypoxia or ischemia and represents an adaptative mechanism in tissue repair. This process is particularly important in physiopathological situations such as wound healing and tumour development. The aim of this study was to characterize the ability of endothelial cells (EA.hy926 endothelial cells line and HUVEC) to undergo morphologic changes in an
in vitro assay after prolonged exposure to hypoxia (3 cycles of 72 hours, 3% O2). We have shown that endothelial cells exposed to hypoxia adapt and proliferate similarly to those under normoxic conditions. Expression of vascular endothelial cell growth factor (VEGF) and its receptors, implicated in vascular response to hypoxia, was studied. Endothelial cells expressed 165 and 121 VEGF receptors KDR was down-regulated during hypoxia. In the second part of this study we attempted to analyse the angiogenic behavior of hypoxic cells in our
in vitro model. We have shown that EA.hy926 and HUVEC cell reorganisation was induced to 50 % after 3 days of hypoxia exposure and this effect was even higher (80 %) in EA.hy926 cells. This effect was not due to modification of endothelial fibrinolytic activity. Moreover, addition of exogeneous VEGF restored cell reorganisation through KDR/Flk receptor signal transduction.
We hypothezise, after analysis of fibrin gel density, that effects of prolonged hypoxia could implicate modifications of cytoskeletal organisation and adhesion molecules expression that permit cell migration and fibrin remodeling.
Keywords:
Endothelial cells, hypoxia,
in vitro assay, VEGF
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