title: Glatiramer acetate (GA) prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.
abstract: Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) is considered to be the major one contributing to the process of development of endothelial dysfunction. Exposure to TNF-α induces the expression of a number of proinflammatory chemokines, such as monocyte chemotactic protein-1 (MCP-1), and adhesion molecules, including vascular adhesion molecule-1 (VCAM-1) and E-selectin, which mediate the interaction of invading monocytes with vascular endothelial cells. Glatiramer acetate (GA) is a licensed clinical drug for treating patients suffering from multiple sclerosis (MS). The effects of GA in vascular disease have not shown before. In this study, we found that GA significantly inhibited TNF-α-induced binding of monocytes to endothelial cells. Mechanistically, we found that GA ameliorated the upregulation of MCP-1, VCAM-1, and E-selectin induced by TNF-α. Notably, this process is mediated by inhibiting the nuclear translocation and activation of NF-κB. Our results also indicate that GA pretreatment attenuates the up-regulation of COX-2 and iNOS. These data suggest that GA might have a potential benefit in therapeutic endothelial dysfunction related diseases.
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, China.
authors.forename: Guoqian
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, China. Electronic address: xueqili075@yeah.net.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Li
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D000068717:Glatiramer Acetate; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D019040:E-Selectin; D016328:NF-kappa B; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000068717:Glatiramer Acetate; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Endothelial dysfunction; Glatiramer acetate; Monocytes adhesion; NF-κB; Tumor necrosis factor-alpha (TNF-α)