The online version of this article (doi:10.1186/1475-2840-11-49) contains supplementary material, which is available to authorized users.
Jia-Shiong Chen, Yung-Hsiang Chen contributed equally to this work.
The authors declare that they have no competing interests.
Jia-Shiong Chen conducted the experiments and contributed to the study implementation, statistical analysis, interpretation, and the preparation of the manuscript. Yung-Hsiang Chen conducted the experiments and contributed to the study conception and design, implementation, and the preparation of the manuscript. Both JS Chen and YH Chen contributed equally to this paper. Po-Hsun Huang and Hsiao-Ya Tsai helped to conduct the experiments and contributed to the study conception and design, implementation, and interpretation. Yuh-Lien Chen contributed to the study conception and design, implementation, and interpretation. Shing-Jong Lin contributed to the study conception and design. Jaw-Wen Chen supervised the study conduction and contributed to the study conception and design, implementation, statistical interpretation, the preparation and finalization of the manuscript. All authors approved the final manuscript for publication.
Chronic elevation of glucose level activates vascular inflammation and increases endothelial adhesiveness to monocytes, an early sign of atherogenesis. This study aimed to elucidate the detailed mechanisms of high-glucose-induced endothelial inflammation, and to investigate the potential effects of Ginkgo biloba extract (GBE), an antioxidant herbal medicine, on such inflammation.
Human aortic endothelial cells were cultured in high glucose or mannitol as osmotic control for 4 days. The expression of cytokines and adhesion molecules and the adhesiveness of endothelial cells to monocytes were examined. The effects of pretreatment of GBE or N-acetylcysteine, an antioxidant, were also investigated.
Either high glucose or mannitol significantly increased reactive oxygen species (ROS) production, interleukin-6 secretion, intercellular adhesion molecule-1 (ICAM-1) expression, as well as endothelial adhesiveness to monocytes. The high-glucose-induced endothelial adhesiveness was significantly reduced either by an anti-ICAM-1 antibody or by an interleukin-6 neutralizing antibody. Interleukin-6 (5 ng/ml) significantly increased endothelial ICAM-1 expression. Piceatannol, a signal transducer and activator of transcription (STAT) 1/3 inhibitor, but not fludarabine, a STAT1 inhibitor, suppressed high-glucose-induced ICAM-1 expression. Pretreatment with GBE or N-acetylcysteine inhibited high-glucose-induced ROS, interleukin-6 production, STAT1/3 activation, ICAM-1 expression, and endothelial adhesiveness to monocytes.
Long-term presence of high glucose induced STAT3 mediated ICAM-1 dependent endothelial adhesiveness to monocytes via the osmotic-related redox-dependent interleukin-6 pathways. GBE reduced high-glucose-induced endothelial inflammation mainly by inhibiting interleukin-6 activation. Future study is indicated to validate the antioxidant/anti-inflammatory strategy targeting on interleukin-6 for endothelial protection in in vivo and clinical hyperglycemia.
Additional file 1 Figure S1.: Pretreatment with GBE had no significant effects on high-glucose-induced AP-1 and NF-κB activation in HEACs. Figure S2. Pretreatment with GBE does-dependently suppressed high glucose-induced ICAM-1 accumulation in HAECs. Figure S3. Endothelial ICAM-1 expression was increased by high-glucose (25 mM) stimulation for 4 days, which was losing after the replacement of normal glucose medium (5 mM) for 1–4 days. (PPT 606 KB)12933_2012_493_MOESM1_ESM.ppt
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- Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways
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