Article
Treatment of endothelial cells with flavonoids modulates transendothelial cell migration
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Published: | April 26, 2013 |
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Introduction: Flavonoids are antioxidant agents currently employed in the treatment of different entities, like cancer or atherosclerosis, to reduce inflammation. Endothelial protective effects of flavonoids have been postulated. We investigated the influence of Venoruton®, hydroxyethyl rutoside, on the transendothelial migration of PBMCs in an experimental inflammation model.
Material and methods: Cells from an immortalized human microvascular endothelial cell line (HMEC) were incubated with different doses (1-5 mmol/well) of hydroxyethyl rutoside (Venoruton®, Novartis Pharma, Nürnberg, Germany) for 1 hour on transwell-filters. Endothelial transmigration of peripheral blood mononuclear cells (PMBC) was assessed in different wells (n=12 in 6 independent experiments) after induction of chemoattraction with 50 ng/ml CXCL12. Incubation without any stimulation was used as control. Expression of ENOS and INOS on HMECs was studied by RT-PCR. Endothelial cells apoptosis was investigated by FACs-Analysis of Annexin V Expression. Statistical analysis was done with one-way ANOVA and Tukey’s post hoc correction.
Results: PMBC transendothelial migration was significantly increased after treatment of HMEC with Venoruton® as compared to untreated controls (Transmigration Index 1 ± 0 vs. 1.093 ± 0.04136; p<0.05). There were no significant differences between chemoattraction and lack of stimuli, though a trend in favor of CXCL12 was observed. Modulation of ENOS/INOS and transmigration after treatment with flavonoids were doses-dependent. Tretament with flavonoids resulted in slightly increased apoptosis of endothelial cells.
Conclusion: Incubation of isolated EC with Venoruton® elevated the transendothelial migration of PMBCs. Furthermore, a doses-dependent action of this flavonoid upon HMECs could be observed. Increase of transendothelial migration is probably related to an activation of the NO-Axis and relaxation of the endothelial cells, a main effect of flavonoids. These findings should be further investigated in a clinical setting.