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.
Highlights
Atherosclerosis is a chronic inflammatory disease of the vessel wall that is related to endothelial cell injury, smooth muscle cell migration and proliferation, platelet activation, and leukocyte accumulation
We reported a decrease in the level of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate-oxidase NOX4, and intercellular adhesion molecule-1 (ICAM-1) in oxidized lowdensity lipoprotein- (ox-LDL-)stimulated Human umbilical vein endothelial cells (HUVECs) [25]
We further investigated the effects of ginkgolide B on vascular permeability and junction protein expression in HUVECs
Summary
Atherosclerosis is a chronic inflammatory disease of the vessel wall that is related to endothelial cell injury, smooth muscle cell migration and proliferation, platelet activation, and leukocyte accumulation. Recent studies have indicated that endothelial cells play a role in regulating leukocyte transmigration under pathological conditions, such as atherosclerosis and oxidative stress, but the underlying mechanisms remain unclear. Studies have indicated that JAM-A may play differential roles in cell-cell adhesion, leukocyte migration, and platelets activation [4, 5]. The gap junction protein Cx43 is enriched in endothelial cells where it may play various biological roles that are unrelated to classic intercellular communication [13, 14]. Previous studies have indicated that the docking of leukocytes to endothelial cells can stimulate the tyrosine phosphorylation of VE-cadherin, resulting in destabilization of the AJ complex and an increase in monolayer permeability [19,20,21].
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