title: Treatment of endothelial cell with flavonoids modulates transendothelial leukocyte migration.
abstract: OBJECTIVE
  This study aimed to investigate the influence of the flavonoid oxerutin (Venoruton®, Novartis, Basel, Switzerland) on endothelial cell apoptosis and transendothelial migration of peripheral blood mononuclear cells and to elucidate the potential mechanisms affecting these processes.
  
  
  METHODS
  Human endothelial cells were treated with Venoruton to assess the potential effect on apoptosis and on the transendothelial migration process. Endothelial nitric oxide synthase and inducible nitric oxide synthase expression in endothelial cell after Venoruton treatment as well as reactive oxygen species levels were analyzed.
  
  
  RESULTS
  Low-dose Venoruton shows a protective effect on endothelial cells and inhibits transendothelial migration of peripheral blood mononuclear cells through an endothelial monolayer, but high-dose Venoruton inversely elevated transendothelial migration of peripheral blood mononuclear cells. Meanwhile, a dose-dependent action of Venoruton on endothelial cell apoptosis could be observed. Endothelial nitric oxide synthase and inducible nitric oxide synthase expression were gradually increased in endothelial cells with increasing Venoruton dosage. In addition, reactive oxygen species were significantly reduced by 0.1 mM and 0.5 mM Venoruton and elevated after high dose treatment.
  
  
  CONCLUSIONS
  These data suggest that the increased transendothelial migration of peripheral blood mononuclear cells is related to the excessive activation of the nitric oxide-axis and subsequent relaxation of the endothelial cells.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany Isabella.Werner@kgu.de.
authors.forename: Isabella
authors.initials: I
authors.lastname: Werner
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Arndh H
authors.initials: AH
authors.lastname: Kiessling
authors.affiliation: Department of Urology, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Juengel
authors.affiliation: Department of Trauma Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Borna
authors.initials: B
authors.lastname: Relja
authors.affiliation: Department of Cardiac Surgery, Chirurgische Klinik Dr. Rinecker, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lamm
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Stock
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Moritz
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Andres
authors.initials: A
authors.lastname: Beiras-Fernandez
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D006896:Hydroxyethylrutoside; C005865:troxerutin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Flavonoids; Venoruton®; apoptosis; nitric oxide-axis; transendothelial migration