Monocyte tissue factor response is decreased in patients with hyperlipidemia
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Published on: October 17, 2017
1Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire and Institut Pasteur Lille, France.
Abstract:
Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001
Insights
Hyperlipidemia impairs monocyte tissue factor (TF) production, a key regulator of blood coagulation. This dysfunction is linked to increased atherogenic lipoproteins, suggesting a novel mechanism in cardiovascular disease development.
Area of Science:
- Hematology
- Cardiovascular Biology
- Immunology
Background:
- Monocytes regulate blood coagulation via tissue factor (TF) and tissue factor pathway inhibitor (TFPI).
- Hyperlipidemia may alter monocyte function, potentially impacting coagulation pathways.
Purpose of the Study:
- To compare TF and TFPI expression in monocytes and plasma TFPI levels between healthy and hyperlipidemic individuals.
- To investigate the relationship between monocyte TF/TFPI expression and plasma lipoproteins.
Main Methods:
- Mononuclear cells were isolated from healthy and hyperlipidemic patients.
- TF and TFPI expression (activity and antigen) were measured in monocytes with and without lipopolysaccharide (LPS) stimulation.
- Plasma TFPI and Factor VII (FVII) levels were quantified.
Main Results:
- LPS-stimulated monocyte TF activity and antigen were significantly lower in hyperlipidemic patients compared to controls.
- Monocyte TF activity showed negative correlations with atherogenic lipoproteins and positive correlations with protective lipoproteins.
- Hyperlipidemic patients exhibited increased plasma TFPI and FVII levels.
Conclusions:
- Hyperlipidemia is associated with impaired TF production by circulating monocytes.
- This impairment is linked to increased atherogenic lipoprotein fractions.
- Further research is needed to understand the underlying mechanisms of this monocyte dysfunction.
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