Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis
2022; Elsevier BV; Volume: 20; Issue: 9 Linguagem: Inglês
10.1111/jth.15777
ISSN1538-7933
AutoresKelley R. Jordan, Cory Wyatt, Meghan E. Fallon, Randy Woltjer, Edward A. Neuwelt, Quifang Cheng, David Gailani, Christina U. Lorentz, Erik I. Tucker, Owen J. T. McCarty, Monica T. Hinds, Khanh P. Nguyen,
Tópico(s)Mast cells and histamine
ResumoJournal of Thrombosis and HaemostasisVolume 20, Issue 9 p. 2035-2045 ORIGINAL ARTICLE Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis Kelley R. Jordan, Kelley R. Jordan orcid.org/0000-0002-7090-0667 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorCory R. Wyatt, Cory R. Wyatt orcid.org/0000-0001-7050-3365 Advanced Imaging Research Center, Portland, Oregon, USASearch for more papers by this authorMeghan E. Fallon, Meghan E. Fallon orcid.org/0000-0002-5868-7576 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorRandy Woltjer, Randy Woltjer orcid.org/0000-0003-0755-9846 Department of Pathology, Portland, Oregon, USASearch for more papers by this authorEdward A. Neuwelt, Edward A. Neuwelt orcid.org/0000-0002-6679-6203 Department of Neurology, Oregon Health & Science University, Portland, Oregon, USASearch for more papers by this authorQuifang Cheng, Quifang Cheng orcid.org/0000-0003-1804-3079 Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorDavid Gailani, David Gailani orcid.org/0000-0001-8142-8014 Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorChristina Lorentz, Christina Lorentz orcid.org/0000-0002-6885-2352 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA Aronora Inc., Portland, Oregon, USASearch for more papers by this authorErik I. Tucker, Erik I. Tucker orcid.org/0000-0003-0532-113X Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA Aronora Inc., Portland, Oregon, USASearch for more papers by this authorOwen J. T. McCarty, Owen J. T. McCarty orcid.org/0000-0001-9481-0124 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorMonica T. Hinds, Monica T. Hinds orcid.org/0000-0002-5267-3376 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorKhanh P. Nguyen, Corresponding Author Khanh P. Nguyen nguykha@ohsu.edu orcid.org/0000-0003-3605-3406 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA VA Portland Health Care System, Portland, Oregon, USA Correspondence Khanh P. Nguyen, Department of Biomedical Engineering, School of Medicine, 3151 SW Sam Jackson Park Road, OP11, 97239 Portland, OR, USA. Email: nguykha@ohsu.eduSearch for more papers by this author Kelley R. Jordan, Kelley R. Jordan orcid.org/0000-0002-7090-0667 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorCory R. Wyatt, Cory R. Wyatt orcid.org/0000-0001-7050-3365 Advanced Imaging Research Center, Portland, Oregon, USASearch for more papers by this authorMeghan E. Fallon, Meghan E. Fallon orcid.org/0000-0002-5868-7576 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorRandy Woltjer, Randy Woltjer orcid.org/0000-0003-0755-9846 Department of Pathology, Portland, Oregon, USASearch for more papers by this authorEdward A. Neuwelt, Edward A. Neuwelt orcid.org/0000-0002-6679-6203 Department of Neurology, Oregon Health & Science University, Portland, Oregon, USASearch for more papers by this authorQuifang Cheng, Quifang Cheng orcid.org/0000-0003-1804-3079 Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorDavid Gailani, David Gailani orcid.org/0000-0001-8142-8014 Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorChristina Lorentz, Christina Lorentz orcid.org/0000-0002-6885-2352 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA Aronora Inc., Portland, Oregon, USASearch for more papers by this authorErik I. Tucker, Erik I. Tucker orcid.org/0000-0003-0532-113X Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA Aronora Inc., Portland, Oregon, USASearch for more papers by this authorOwen J. T. McCarty, Owen J. T. McCarty orcid.org/0000-0001-9481-0124 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorMonica T. Hinds, Monica T. Hinds orcid.org/0000-0002-5267-3376 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USASearch for more papers by this authorKhanh P. Nguyen, Corresponding Author Khanh P. Nguyen nguykha@ohsu.edu orcid.org/0000-0003-3605-3406 Department of Biomedical Engineering, School of Medicine, Portland, Oregon, USA VA Portland Health Care System, Portland, Oregon, USA Correspondence Khanh P. Nguyen, Department of Biomedical Engineering, School of Medicine, 3151 SW Sam Jackson Park Road, OP11, 97239 Portland, OR, USA. Email: nguykha@ohsu.eduSearch for more papers by this author First published: 31 May 2022 https://doi.org/10.1111/jth.15777 Manuscript handled by: Roger Preston Final decision: Roger Preston, 25 May 2022 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract 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. CONFLICTS OF INTEREST Drs. Lorentz, Tucker, and the Oregon Health & Science University have a significant financial interest in Aronora, Inc., a company that may have a commercial interest in the results of this research. This potential conflict of interest has been reviewed and managed by the Oregon Health & Science University Conflict of Interest in Research Committee. The remaining authors declare no competing financial interests. Supporting Information Filename Description jth15777-sup-0001-FigureS1.tifimage/tif, 221.8 KB Figure S1 jth15777-sup-0002-FigureS2.tifimage/tif, 901.3 KB Figure S2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume20, Issue9September 2022Pages 2035-2045 RelatedInformation
Referência(s)