β2-Glycoprotein I inhibits VEGF-induced endothelial cell growth and migration via suppressing phosphorylation of VEGFR2, ERK1/2, and Akt

• Published in: Molecular and cellular biochemistry 2013, Vol.372 (1-2), p.9-15
• Main Authors: Chiu, Wen-Chin, Lin, Jan-Yu, Lee, Tzong-Shyuan, You, Li-Ru, Chiang, An-Na
• Format: Article
• Language: English
• Subjects: Aorta - cytology; beta 2-Glycoprotein I - physiology; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Movement; Cell Proliferation; Cells, Cultured; Endothelial Cells - metabolism; Endothelial Cells - physiology; Endothelium, Vascular - cytology; Gene Expression; Humans; Life Sciences; Medical Biochemistry; Neovascularization, Pathologic - metabolism; Oncology; Phosphorylation; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases - metabolism; Vascular Endothelial Growth Factor A - physiology; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1440-6

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.