Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 218, Issue -, Pages 188-195Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2016.04.177
Keywords
Atherosclerosis; Inflammation; T-lymphocyte; Tissue factor; Thrombosis
Categories
Funding
- PRIN (Progetti di Ricerca di InteresseNazionale) from MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca) [2009FJX9KW]
- Ministry of Health (Young Researcher Grant) [GR-2011-02347781]
- Mario e Valeria Rindi fellowship of the Italian Foundation for Cancer Research
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Objective: T-lymphocyte activation plays an important role in the pathophysiology of acute coronary syndromes (ACS). Plaques from ACS patients show a selective oligoclonal expansion of T-cells, indicating a specific, antigen-driven recruitment of T-lymphocytes within the unstable lesions. At present, however, it is not known whether T-cells may contribute directly to thrombosis by expressing functional tissue factor (TF). Accordingly, the aim of the present study was to investigate whether T-cells are able to express functional TF in their activated status. Methods: In vitro, CD3(+)-cells, isolated from buffy coats, were stimulated with anti-CD3/CD28 beads, IL-6, TNF-alpha, IL-17, INF-gamma or PMA/ionomycin. Following stimulation, TF expression on cell-surface, at gene and protein levels, as well as its procoagulant activity in whole cells and microparticles was measured. In vivo, TF expression was evaluated in CD3(+)-cells isolated from the aorta and the coronary sinus of ACS-NSTEMI and stable coronary artery disease (SCAD) patients. The presence of CD3(+)-TF+ cells was also evaluated by immunohistochemistry in thrombi aspirated from ACS-STEMI patients. Results: PMA/ionomycin and IL-17 plus INF-gamma stimulation resulted in a significant TF increase at gene and protein levels as well as at cell-surface expression. This was accompanied by a parallel increase in FXa generation, both in whole cells and in microparticles, indicating that the induced membrane-bound TF was active. Furthermore, transcardiac TF gradient was significantly higher in CD3(+)-cells obtained from ACS-patients compared to SCAD-patients. Interestingly, thrombi from ACS-STEMI patients resulted enriched in CD3(+)-cells, most of them expressing TF. Conclusions: Our data demonstrate that activated T-lymphocytes in vitro express functional TF on their membranes, suggesting a direct pathophysiological role of these cells in the thrombotic process; this hypothesis is further supported by the observations in vivo that CD3(+)-cells from coronary circulation of ACS-NSTEMI patients show increased TF levels and that coronary thrombi from ACS-STEMI patients are enriched in CD3(+)-cells expressing TF. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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