Methyl-Beta-Cyclodextrin Suppresses The Monocyte-Endothelial Adhesion Triggered By Lipopolysaccharide (Lps) Or Oxidized Low-Density Lipoprotein (Oxldl)

Context Recent studies demonstrated the anti-atherosclerotic efficacy of cyclodextrin. However, it remains unclear whether cyclodextrin exerts the anti-atherosclerotic effect via regulating monocyte-endothelial adhesion.Objective To answer that question by recruiting methyl-beta-cyclodextrin (M beta CD) as a cyclodextrin representative.Materials and methods Human umbilical vein endothelial cells (HUVECs) were not treated, or treated with 1 mu g/mL liposaccharide (LPS) or 50 mu g/mL oxidized low-density lipoprotein (oxLDL) for 12 h, 5 mM M beta CD for 1 h, and LPS/oxLDL (1 and 50 mu g/mL, respectively for 12 h) plus M beta CD (5 mM for 1 h), respectively. The effects of M beta CD on LPS/oxLDL-triggered monocyte-endothelial adhesion and related molecules in signalling pathways were evaluated via confocal microscopy, flow cytometry, RT-PCR, western blotting, and cell adhesion assay.Results M beta CD with an IC50 of 27.66 mM (1 h treatment) exerted no significant cytotoxicity at <= 5 mM for <= 2 h. Compared with the control, both LPS and oxLDL induced an similar to 2-3-fold increase in adhesion molecule expression (ICAM-1 and VCAM-1 at protein and mRNA levels) and NF-kappa B phosphorylation (p-NF-kappa B/pP65), an increase in I kappa B kinase (IKK), and a decrease in phosphorylated protein kinase B (p-Akt), respectively. Moreover, more monocytes (2-fold higher for LPS and 15% higher for oxLDL) were attached on LPS/oxLDL-stimulated HUVECs. 5 mM M beta CD reversed the LPS/oxLDL-induced changes back to the control levels.Conclusions M beta CD significantly suppresses the LPS/oxLDL-triggered monocyte-endothelial adhesion by downregulating adhesion molecule expression probably via LPS-IKK-NF-kappa B or oxLDL-Akt-NF-kappa B pathway. This study demonstrates a potential mechanism of the anti-atherosclerotic efficacy of cyclodextrin from the angle of monocyte-endothelial adhesion.