Tissue Factor encryption and decryption: Facts and controversies

Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Thrombosis Research (Impact Factor: 2.45). 03/2012; 129 Suppl 2:S13-7. DOI: 10.1016/j.thromres.2012.02.021
Source: PubMed

ABSTRACT Tissue factor (TF)-initiated coagulation plays a critical role in both hemostasis and thrombosis. It is generally believed that most of the tissue factor expressed on cell surfaces is maintained in a cryptic, i.e., coagulantly inactive state and an activation step (decryption) is required for the expression of maximum TF procoagulant activity. However, what exactly constitutes cryptic or procoagulant TF, molecular differences between these two forms and mechanisms that are responsible for transformation from one to the other form are not entirely clear and remain highly controversial, thus are a matter of ongoing debate. This brief review discusses pertinent literature on TF encryption/decryption with specific emphasis on the role of membrane phospholipids and reduction/oxidation of the TF Cys186-Cys209 disulfide bond in regulating TF activity at cell surfaces.

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Available from: Hema Kothari, Sep 28, 2015
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    • "It is generally believed that most TF on the surfaces of cells surrounding blood vessels exist in a state with very little procoagulant activity and must undergo a transformation to become fully active [34]. The aberrant activation of TF-mediated coagulation leads to intravascular thrombus formation. "
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    ABSTRACT: Injured endothelium is an important target for drug and/or gene therapy because brain microvascular endothelial cells (BMECs) play critical roles in various pathophysiological conditions. RNA-mediated gene silencing presents a new therapeutic approach for treating such diseases, but major challenge is to ensure minimal toxicity and target delivery of siRNA to injured BMECs. Injured BMECs overexpress tissue factor (TF), which the fusion protein EGFP-EGF1 could be targeted to. In this study, TNF alpha (TNF-α) was chosen as a stimulus for primary BMECs to produce injured endothelium in vitro. The EGFP-EGF1-PLGA nanoparticles (ENPs) with loaded TF-siRNA were used as a new carrier for targeted delivery to the injured BMECs. The nanoparticles then produced intracellular RNA interference against TF. We compared ENP-based transfections with NP-mediated transfections, and our studies show that the ENP-based transfections result in a more efficient downregulation of TF. Our findings also show that the TF siRNA-loaded ENPs had minimal toxicity, with almost 96% of the cells viable 24 h after transfection while Lipofectamine-based transfections resulted in only 75% of the cells. Therefore, ENP-based transfection could be used for efficient siRNA transfection to injured BMECs and for efficient RNA interference (RNAi). This transfection could serve as a potential treatment for diseases, such as stroke, atherosclerosis and cancer.
    PLoS ONE 04/2013; 8(4):e60860. DOI:10.1371/journal.pone.0060860 · 3.23 Impact Factor
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    • "This complex is able to activate FX, which in turn results in thrombin, which is responsible for thrombus stabilization (Monroe et al., 2002). Moreover, membrane-embedded TF is usually in inactive coagulant state (cryptic) while it requires activation to reach its full potency (decryption) (Rao et al., 2012). However, the mechanism behind the activation of circulating TF is not yet elucidated and such information would provide a significant breakthrough in the understanding of in vivo thrombosis. "
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    ABSTRACT: The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET) release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis, and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.
    Frontiers in Immunology 12/2012; 3:385. DOI:10.3389/fimmu.2012.00385
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    ABSTRACT: Tissue factor (TF) is the high affinity receptor for factor VII (FVII)/VIIa [1]. It is expressed by cells surrounding blood vessels and in certain tissues and is required for hemostasis [2]. During Gram-negative bacterial infection, lipopolysaccharide (LPS) induces TF expression in circulating monocytes [3-5] resulting in local clot formation to immobilize the bacterium and limit the spread of the infection. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 07/2012; 10(9):1965-7. DOI:10.1111/j.1538-7836.2012.04842.x · 5.72 Impact Factor
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