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Published on: October 17, 2017
CD14+-Monocytes Exposed to Apolipoprotein CIII Express Tissue Factor
Oliviero Olivieri1, Sara Gasperini2, Federica Calzetti2
1Unit of Internal Medicine, Department of Medicine, University of Verona, 37134 Verona, Italy.
Insights
Apolipoprotein CIII (ApoCIII) activates monocytes to express tissue factor (TF), a key initiator of blood clotting. This finding links ApoCIII to inflammation and atherothrombosis, contributing to cardiovascular disease risk.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Immunology
Background:
- Apolipoprotein CIII (ApoCIII) is a critical regulator of plasma lipid metabolism and a risk factor for cardiovascular diseases.
- ApoCIII contributes to endothelial dysfunction and monocyte recruitment in atherothrombosis.
Purpose of the Study:
- To investigate whether ApoCIII induces tissue factor (TF) expression in monocytes.
- To explore the role of ApoCIII in monocyte activation and its link to atherothrombosis.
Main Methods:
- Human CD14+ monocytes and neutrophils were incubated with purified ApoCIII and human sera.
- Gene expression (RT-qPCR) and protein production (ELISA) of inflammatory cytokines and TF were measured.
- TF surface expression on monocytes was analyzed by flow cytometry.
- The effect of ApoCIII-neutralizing antibodies on TF expression was assessed.
Main Results:
- ApoCIII exposure significantly increased mRNA and protein levels of TNFα, IL-1β, IL-6, and TF in CD14+ monocytes, but not neutrophils.
- Monocytes rapidly expressed cell-surface TF upon incubation with ApoCIII or ApoCIII-containing sera.
- ApoCIII-neutralizing antibodies partially inhibited TF upregulation and cytokine release in monocytes.
Conclusions:
- Apolipoprotein CIII activates human CD14+ monocytes to express tissue factor.
- This mechanism connects circulating apolipoproteins to inflammation and atherothrombosis, highlighting a novel pathway in cardiovascular risk.
Abstract:
Apolipoprotein CIII (ApoCIII) represents a key regulator of plasma lipid metabolism and a recognized risk factor for atherosclerosis and cardiovascular diseases. Beyond the regulation of lipoprotein trafficking, ApoCIII is also involved in endothelial dysfunction and monocyte recruitment related to atherothrombosis. With tissue factor (TF) being the primary initiator of the blood coagulation cascade, we hypothesized that ApoCIII-treated monocytes could express it. Hence, human CD14+-monocytes and autologous neutrophils were incubated with ApoCIII and sera from human subjects containing previously measured ApoCIII amounts. By RT-qPCR and ELISA, CD14+-monocytes, but not neutrophils, were found to show increased mRNA expression and production of TNFα, IL-1β and IL-6 as well as TF mRNA once exposed to ultra-purified ApoCIII. By flow cytometry, CD14+-monocytes were found to rapidly express TF on their cell surface membrane when incubated with either ApoCIII or sera with known concentrations of ApoCIII. Finally, preincubation with specific ApoCIII-neutralizing antibodies significantly reduced the ability of most sera with known concentrations of ApoCIII to upregulate TF protein, other than partially inhibiting cytokine release, in CD14+-monocytes. In sum, herein we demonstrate that ApoCIII activates CD14+-monocytes to express TF. The data identify a potential mechanism which links circulating apolipoproteins with inflammation and atherothrombosis-related processes underlying cardiovascular risk.
