Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis
Background Deep vein thrombosis (DVT) and post‐thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti‐factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI with...
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Published in | Journal of thrombosis and haemostasis Vol. 20; no. 9; pp. 2035 - 2045 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.09.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Background
Deep vein thrombosis (DVT) and post‐thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti‐factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis. The human recombinant analog, AB023, is in clinical development. The role of FXI in mediation of inflammation during DVT resolution is unknown.
Objectives
Investigate the effects of pharmacological targeting of FXI with 14E11 in an experimental model of venous thrombosis.
Methods
Adult wild‐type CD1 mice were treated with subcutaneous anti‐FXI antibody (14E11, 5 mg/kg) versus saline prior to undergoing surgical constriction of the inferior vena cava (IVC). Mice were evaluated at various time points to assess thrombus weight and volume, as well as histology analysis, ferumoxytol enhanced magnetic resonance imaging (Fe‐MRI), and whole blood flow cytometry.
Results
14E11‐treated mice had reduced thrombus weights and volumes after IVC constriction on day 7 compared to saline‐treated mice. 14E11 treatment reduced circulating monocytes by flow cytometry and macrophage content within thrombi as evaluated by histologic staining and Fe‐MRI. Collagen deposition was increased at day 3 while CD31 and smooth muscle cell actin expression was increased at day 7 in the thrombi of 14E11‐treated mice compared to saline‐treated mice.
Conclusion
Pharmacologic targeting of FXI enhances the early stages of experimental venous thrombus resolution in wild‐type CD1 mice, and may be of interest for future clinical evaluation of the antibody in DVT and PTS. |
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Bibliography: | Final decision: Roger Preston, 25 May 2022 Manuscript handled by: Roger Preston ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1538-7933 1538-7836 1538-7836 |
DOI: | 10.1111/jth.15777 |