Dose-dependent modulation of tissue factor protein and procoagulant activity in human monocyte-derived macrophages by oxidized low density lipoprotein
SR Meisel, XP Xu, TS Edgington, B Cercek… - … of atherosclerosis and …, 2011 - jstage.jst.go.jp
SR Meisel, XP Xu, TS Edgington, B Cercek, J Ong, S Kaul, PK Shah
Journal of atherosclerosis and thrombosis, 2011•jstage.jst.go.jpAim: Oxidized low-density lipoprotein (oxLDL) interacts with macrophages and is implicated
in atherogenesis. Macrophages are also the major source within the atherosclerotic plaque
of tissue factor (TF), the membrane-bound glycoprotein receptor that triggers the coagulation
cascade in vivo and contributes to plaque thrombogenicity. In this study we tested the
hypothesis that oxLDL modulates TF expression in human monocyte-derived macrophages
(MDMs). Methods: Mononuclear cells were isolated from human blood, allowed to …
in atherogenesis. Macrophages are also the major source within the atherosclerotic plaque
of tissue factor (TF), the membrane-bound glycoprotein receptor that triggers the coagulation
cascade in vivo and contributes to plaque thrombogenicity. In this study we tested the
hypothesis that oxLDL modulates TF expression in human monocyte-derived macrophages
(MDMs). Methods: Mononuclear cells were isolated from human blood, allowed to …
抄録
Aim: Oxidized low-density lipoprotein (oxLDL) interacts with macrophages and is implicated in atherogenesis. Macrophages are also the major source within the atherosclerotic plaque of tissue factor (TF), the membrane-bound glycoprotein receptor that triggers the coagulation cascade in vivo and contributes to plaque thrombogenicity. In this study we tested the hypothesis that oxLDL modulates TF expression in human monocyte-derived macrophages (MDMs).
Methods: Mononuclear cells were isolated from human blood, allowed to differentiate into MDMs during 8 days in cell culture, and then exposed to varying concentrations of oxLDL in the presence or absence of lipopolysaccharide (LPS). TF procoagulant activity (TF-PCA) of MDMs was measured by one-stage recalcification clotting assay using human recombinant TF as standard. TF protein was evaluated by Western blotting, and TF mRNA was determined by Northern blot analysis.
Results: OxLDL at 5-10 µg/mL increased TF-PCA, TF protein, and mRNA in MDMs, whereas 20-100 µg/mL oxLDL inhibited TF-PCA, protein expression, and mRNA expression in these cells even in the face of LPS stimulation.
Conclusions: Low concentrations of oxLDL enhance TF expression in MDMs, whereas higher concentrations attenuate TF expression both at baseline as well as following LPS stimulation. Both TF-PCA and TF protein follow this dose-response pattern that is preceded by concordant mRNA changes. Thus, we have demonstrated modulation by oxLDL of TF protein and bioactivity in MDMs.
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