The mechanism of oxLDL/β2GPI/anti-β2GPI antibody complex promoting the expression of adhesion molecules in HUVECs

Objective To investigate the effect of oxidative low-density lipoprotein/β2 glycoprotein I/anti-β2 glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI-Ab) complex on the expressions of adhesion molecules in human umbilical vein endothelial cells (HUVECs), and the role of Toll-like receptor 4 (TLR4) signaling pathway during this process. Methods HUVECs were stimulated with simple medium, oxLDL, oxLDL/β2GPI complex, oxLDL/anti-β2GPI-Ab complex, oxLDL/β2GPI/anti-β2GPI-Ab complex and LPS separately, and then the total mRNA and protein were collected. The mRNA and protein expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and von Willebrand factor (vWF) were detected by real-time quantitative PCR and Western blotting, respectively. Pre-treatment method was applied to explore the influence of TLR4 antagonist TAK-242 (5 μmol/L) and p38MAPK antagonist SB203580 (10 μmol/L) on the expressions of adhesion molecules in HUVECs. THP-1 cell adhesion test was employed to evaluate the effect of oxLDL/β2GPI/anti-β2GPI-Ab complex on the ability of attracting monocytes of HUVECs. Results Compared with simple medium, oxLDL/β2GPI/anti-β2GPI-Ab complex obviously upregulated the expressions of ICAM-1, VCAM-1 and vWF in HUVECs and promoted the adhesion of THP-1 cells to HUVECs. In addition, these effects were inhibited by the pre-treatment of TAK-242 or SB203580. Conclusion OxLDL/β2GPI/anti-β2GPI-Ab complex could up-regulate the expressions of adhesion molecules in HUVECs and promote the adhesion of THP-1 cells to HUVECs, in which TLR4 and p38 MAPK were closely involved.