Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells

Oxid Med Cell Longev. 2015:2015:907926. doi: 10.1155/2015/907926. Epub 2015 Jul 12.

Abstract

Aim: 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.

Conclusion: Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Cadherins / metabolism*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chromones / pharmacology
  • Connexin 43 / metabolism*
  • Gene Expression Regulation / drug effects*
  • Ginkgolides / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Junctional Adhesion Molecule A / metabolism*
  • Lactones / pharmacology*
  • Lipoproteins, LDL / toxicity*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Morpholines / pharmacology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • Chromones
  • Connexin 43
  • Ginkgolides
  • Junctional Adhesion Molecule A
  • Lactones
  • Lipoproteins, LDL
  • Morpholines
  • cadherin 5
  • oxidized low density lipoprotein
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • ginkgolide B
  • Proto-Oncogene Proteins c-akt