Abstract Number: OC 17.2
Meeting: ISTH 2021 Congress
Background: Coagulation factor (F) V is an important cofactor of the prothrombinase complex, but was recently shown to possess coagulation-independent effects related to inflammatory signalling. Inflammation is a driver of atherosclerotic disease and although other coagulation proteins have been identified in atherosclerotic plaques, little is known about FV.
Aims: To elucidate the role of FV in atherosclerotic plaques.
Methods: 167 human carotid plaques retrieved by endarterectomy and 14 non-atherosclerotic common iliac arteries of deceased donors were homogenized and lysed for mRNA or protein detection. Plasma was collected from 250 endarterectomy patients and 92 age- and sex-matched controls. Primary human PBMCs from blood donors were incubated with M-CFS for 6 days before treatment with oxidized low density lipoprotein (LDL) at different concentrations for 24 hours. Relative F5 mRNA quantification was performed using qRT-PCR and FV protein was detected by ELISA, Western blotting, or immunohistochemistry.
Results: Both F5 mRNA and FV protein were detected in the carotid plaques. The mRNA expression was upregulated 3.3-folds in the plaques compared to the control arteries. The mean FV protein level in plaques was 78.8 ng/mg total protein and did not correlate with symptomatic state.
Both native and active FV was detected in the plaque samples. There was no difference in FV plasma levels between patients and controls, indicating that FV levels were not systemically affected. F5 mRNA expression correlated significantly with expression of the immune cell markers CD14, CD163, CD45, and NLRP3, and FV protein co-localized with macrophage marker Mac2 in the plaques. Oxidized LDL treatment increased FV levels in human PBMC-derived macrophages in a dose-dependent manner.
Conclusions: These data show that coagulation FV is produced by cells in human carotid plaques and indicate an association between FV and immune cells in atherosclerotic disease. Thus, FV could be an interesting link between the inflammation-driven disease burden and the procoagulant plaque.
To cite this abstract in AMA style:Stavik B, Seierstad Andresen M, Holm S, Skjelland M, Tinholt M, Sandset PM, Iversen N, Halvorsen B. Increased Levels of Coagulation Factor V in Atherosclerotic Plaques – An Immune Regulated Response? [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/increased-levels-of-coagulation-factor-v-in-atherosclerotic-plaques-an-immune-regulated-response/. Accessed October 1, 2023.
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