Abstract
Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures.
Highlights
Deep vein thrombosis (DVT) affects approximately 2,000,000 people in the US each year [1,2]
Thrombus weight at day 4 after the vena cava ligation is considered a measure of thrombus formation, whereas thrombus weight at 12 days is used as a measure of thrombus resolution in this model
We investigated the functional role of T cells in venous thrombosis by comparing venous thrombus formation induced by vena cava ligation between animals treated with both anti-CD4 and anti-CD8 antibodies or isotype matched antibodies (Figure 2A)
Summary
Deep vein thrombosis (DVT) affects approximately 2,000,000 people in the US each year [1,2]. It significantly affects quality of life in patients and is a major burden to health care costs [3,4]. Current treatment for DVT involves anticoagulation, which effectively prevents propagation of the existing thrombus as well as new thrombus formation but fails to resolve already formed thrombus [10,11,12]. Despite the use of anticoagulants, approximately 25% to 50% of DVT patients develop PTS [13,14], whereas about 5% of patients suffering from an unresolved PE develop CTEPH as a late complication [15]. The lack of specific therapeutic options for these debilitating complications of DVT warrants a better cellular and molecular understanding of the process of venous thrombus formation and resolution
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
