Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2574477 | Vascular Pharmacology | 2010 | 9 Pages |
Recent evidence showed that 17 β-estradiol (E2) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca2+ concentration ([Ca2+]i) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E2 (1 μM, 24 h) on the expression of intracellular adhesion molecule-1 (ICAM-1) and [Ca2+]i were investigated in a lipopolysaccharide (LPS) (100 ng/mL, 18 h)-stimulated human endothelial cell line, EA.hy926, using real-time PCR and spectrofluorometry, respectively. PCR analysis revealed a significant increase in ICAM-1 expression in calcium ionophore A23187 (1 nM)- or LPS-stimulated cells. Pretreatment of cells with E2 significantly inhibited LPS-induced ICAM-1 mRNA expression. [Ca2+]i was monitored in Fura-2 AM-loaded cells in the presence and absence of extracellular Ca2+ with thapsigargin (TG, 1 μM), a sarco/endoplasmic reticulum ATPase inhibitor or ATP (100 μM). The extent of TG- or ATP-induced [Ca2+]i increase was significantly higher in LPS-stimulated cells than in control cells. Pre-treatment of LPS-stimulated cells with E2 limited the Ca2+ response to the same level as in control cells. Furthermore, ICI 182,780, an estrogen receptor antagonist, attenuated the inhibitory actions of E2 on ICAM-1 mRNA expression and Ca2+ responses, suggesting that estrogen receptors mediate, at least in part, the effects of estrogen. These data suggest a potential underlying mechanism for the protective effect of E2 against atherosclerosis.
Graphical abstract• In the early stages of atherosclerosis, inflammatory cells are recruited to vascular wall via CAM.• Estrogen's effect on CAM and a possible link between CAM and Ca2+ contribute to the hypothesis that the anti‐atherogenic effect of E2 is mediated, in part, by the modulatory effects on Ca2+.Figure optionsDownload full-size imageDownload as PowerPoint slide