title: β₂-glycoprotein I inhibits VEGF-induced endothelial cell growth and migration via suppressing phosphorylation of VEGFR2, ERK1/2, and Akt.
abstract: β(2)-glycoprotein I (β(2)-GPI) is a plasma glycoprotein with diverse functions, but the impact and molecular effects of β(2)-GPI on vascular biology are as yet unclear. Based on the limited information available on the contribution of β(2)-GPI to endothelial cells, we investigated the effect of β(2)-GPI on cell growth and migration in human aortic endothelial cells (HAECs). The regulation of β(2)-GPI as part of intracellular signaling in HAECs was also examined. Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that may regulate endothelial functions. We found that β(2)-GPI dose-dependently inhibited VEGF-induced endothelial cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-dipenyl tetrazolium bromide assay and cell counts. Using wound healing and Boyden chamber assays, β(2)-GPI remarkably reduced VEGF-increased cell migration at the physiological concentration. Furthermore, β(2)-GPI suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2), extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt. These results suggest that β(2)-GPI plays an essential role in the down-regulation of VEGF-induced endothelial responses and may be a useful component for anti-angiogenic therapy.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155 Section 2, Li-Nong Street, Shih-Pai, Taipei 11221, Taiwan, Republic of China.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Chiu
authors.forename: Jan-Yu
authors.initials: JY
authors.lastname: Lin
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: You
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
mesh_terms: D001011:Aorta / Q000166:cytology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000502:physiology*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053482:beta 2-Glycoprotein I; D040301:Vascular Endothelial Growth Factor Receptor-2; D017346:Protein Serine-Threonine Kinases