Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment

Yu, Yuanjie; Böing, Anita N.; Hau, Chi M.; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

doi:10.1055/s-0038-1642031

Cited by 11 publications

(9 citation statements)

References 36 publications

(59 reference statements)

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“…Thus, although they have substantially different roles in coagulation mechanism, their increase in blood reflects systematic endothelial cell activation [24]. Release of TFPI and thrombomodulin by activated endothelial cells deprives vascular microenvironment of important inhibitors of TF and thrombin generation [25]. Heparanase, an endo-β-D-glucuronidase, stems from activated endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Gerotziafas

Dreden

Sergentanis

et al. 2022

Hemato

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Background. Hypercoagulable state and endothelial cell activation are common alterations in patients with COVID-19. Nevertheless, the hypothesis of persistent hypercoagulability and endothelial cell activation following recovery from COVID-19 remains an unresolved issue. Objectives. To investigate the persistence of endothelial cell activation and hypercoagulability after recovery from COVID-19. Patients/Methods. COVID-19 survivors (n = 208) and 30 healthy individuals were enrolled in this study. The following biomarkers were measured: procoagulant phospholipid-dependent clotting time (PPL-ct), D-Dimer, fibrin monomers (FM), free Tissue factor pathway inhibitor (free-TFP)I, heparinase, and soluble thrombomodulin (sTM). Antibodies against SARS-CoV-2 (IgG and IgA) were also measured. Results. The median interval between symptom onset and screening for SARS-CoV-2 antibodies was 62 days (IQR = 22 days). Survivors showed significantly higher levels of D-Dimers, FM, TFPI, and heparanase as compared to that of the control group. Survivors had significantly shorter PPL-ct. Elevated D-dimer was associated with older age. Elevated FM was associated with female gender. Elevated heparanase was independently associated with male gender. Decreased Procoag-PPL clotting time was associated with female gender. One out of four of COVID-19 survivors showed increase at least one biomarker of endothelial cell activation or hypercoagulability. Conclusions. Two months after onset of COVID-19, a significant activation of endothelial cells and in vivo thrombin generation persists in at least one out of four survivors of COVID-19. The clinical relevance of these biomarkers in the diagnosis and follow-up of patients with long COVID-19 merits to be evaluated in a prospective clinical study.

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Section: Discussionmentioning

confidence: 99%

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Gerotziafas

Dreden

Sergentanis

et al. 2022

Hemato

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“…By putting the total protein content of SEC fractions on blot, the absolute presence of a protein of interest can be compared between fractions as described earlier. 22 Both CD63 and CD9 were below the detection limit in milk, the starting material ( Figure 2A-B, respectively), whereas TF was clearly detectable ( Figure 3A). The supernatant and resuspended pellet together with SEC fractions were used for flow cytometry, surface plasmon resonance imaging, western blot, and clotting assay, respectively.…”

Section: Isolation Of Evs From Human Milkmentioning

confidence: 95%

Human milk triggers coagulation via tissue factor–exposing extracellular vesicles

Hell²,

Kendlbacher³

et al. 2020

Blood Advances

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Almost a century ago, it was discovered that human milk activates the coagulation system, but the milk component that triggers coagulation had until now been unidentified. In the present study, we identify this component and demonstrate that extracellular vesicles (EVs) present in normal human milk expose coagulant tissue factor (TF). This coagulant activity withstands digestive conditions, mimicking those of breastfed infants, but is sensitive to pasteurization of pooled donor milk, which is routinely used in neonatal intensive care units. In contrast to human milk, bovine milk, the basis of most infant formulas, lacks coagulant activity. Currently, the physiological function of TF-exposing vesicles in human milk is unknown, but we speculate that these vesicles may be protective for infants. Another explanation could be nipple skin damage, which occurs in most breastfeeding women. Milk-derived TF-exposing EVs may seal the wound and thereby reduce bleeding and breast inflammation.

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“…Exosomes can affect vascular endothelial cell function as well as platelet activation and aggregation, increasing blood coagulability (7). Vascular endothelial cells play an important role in the stabilization of blood flow, and procoagulant factors secreted by endothelial cells directly and quickly participate in coagulation and thrombosis (8).…”

Section: Original Articlementioning

confidence: 99%

Exosomal myeloperoxidase as a biomarker of deep venous thrombosis

Han¹,

Bai²,

Wang³

2022

Ann Transl Med

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Background: Deep vein thrombosis (DVT) often occurs following major orthopedic surgery. In this study, we investigated specific exosomal proteins as potential diagnostic biomarkers of DVT.Methods: Proteomic analysis of exosomes from four DVT patients and healthy controls (n=4) was performed by mass spectrometry. The model animals were evaluated at 1 inferior vena cava ligation [(IVCL)-1D], 3 (IVCL-3D), and 7 (IVCL-7D) days after IVCL. Endothelial cells in the thrombus segment were examined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and hematoxylin and eosin (HE) staining. Myeloperoxidase (MPO) expression in the damaged vessel was detected by immunofluorescence staining. Exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) and cell proliferation was estimated using Cell Counting Kit-8 (CCK-8) assays.Results: A total of 78 differentially expressed proteins (DEPs; 38 downregulated and 40 upregulated) were identified in the DVT group. In the rat DVT model, endothelial cells were damaged continuously after thrombosis, with the most serious injury in the IVCL-3D group, after which signs of endothelial repair were apparent. The IVCL-1D group showed the highest levels of vascular endothelial cell apoptosis and MPO increased sharply in the IVCL-1D and IVCL-3D groups, but had almost disappeared in the IVCL-7D group. In co-culture, plasma exosomes isolated from DVT model rats were efficiently absorbed by HUVECs, with markedly lower HUVECs growth and higher levels of apoptosis in the IVCL-1D and IVCL-3D groups compared with the control group.Conclusions: Our findings suggest that exosomes may be involved in endothelial cell injury during DVT.The exosomal protein MPO is a potential biomarker of early stage DVT.

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Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment

Abstract: Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity.

Cited by 11 publications

References 36 publications

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Persisting Endothelial Cell Activation and Hypercoagulability after COVID-19 Recovery—The Prospective Observational ROADMAP-Post COVID-19 Study

Human milk triggers coagulation via tissue factor–exposing extracellular vesicles

Exosomal myeloperoxidase as a biomarker of deep venous thrombosis

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