title: Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells.
abstract: OBJECTIVE
  To investigate the effect of ginkgolide B on junction proteins and the reduction of monocyte migration in oxidized low-density lipoprotein- (ox-LDL-) treated endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were used in the present study. Immunofluorescence and Western blot were performed to determine the expression of junctional adhesion molecule-A (JAM-A), connexin 43 (Cx43), and vascular endothelial cadherin (VE-cadherin). Monocyte migration was detected by the Transwell assay.
  
  
  RESULTS
  ox-LDL stimulation increased JAM-A expression by 35%, Cx43 expression by 24%, and VE-cadherin expression by 37% in HUVECs. Ginkgolide B (0.2, 0.4, and 0.6 mg/mL) dose-dependently abolished the expression of these junction proteins. The monocyte transmigration experiments showed that the level of monocyte migration was sixfold higher in the ox-LDL-treated group than in the control group. Ginkgolide B (0.6 mg/mL) nearly completely abolished monocyte migration. Both ginkgolide B and LY294002 suppressed Akt phosphorylation and the expression of these junction proteins in ox-LDL-treated endothelial cells. These results suggest that the ginkgolide B-induced inhibition of junction protein expression is associated with blockade of the PI3K/Akt pathway.
  
  
  CONCLUSIONS
  Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis.
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Sun
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Beidong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bao
authors.affiliation: Beijing Institute of Geriatrics, Beijing Hospital and Key Laboratory of Geriatrics Ministry of Health, Beijing 100730, China.
authors.forename: Ruomei
authors.initials: R
authors.lastname: Qi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D046934:Ginkgolides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D062745:Junctional Adhesion Molecule A / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000633:toxicity*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D002867:Chromones; D018031:Connexin 43; D046934:Ginkgolides; D062745:Junctional Adhesion Molecule A; D007783:Lactones; D008077:Lipoproteins, LDL; D009025:Morpholines; D051057:Proto-Oncogene Proteins c-akt; D000099152:Cadherin 5; C099252:oxidized low density lipoprotein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C045856:ginkgolide B