Tissue factor-bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer

© 2017 International Society on Thrombosis and Haemostasis Summary: Cancer is associated with an increased risk of venous thromboembolism (VTE); the exact mechanisms for the induction of VTE remain to be fully elucidated, but it is widely acknowledged that tissue factor (TF)-bearing microparticles (TF-MPs) may play a significant role. However, TF-MPs have yet to be accepted as a genuine biomarker for cancer-associated VTE, as the presence of elevated TF-MP levels is not always accompanied by thrombosis; interestingly, in certain cases, particularly in pancreatic cancer, VTE seems to be more likely in the context of acute inflammation. Although several potential mechanisms for the development of VTE in cancer have been postulated, this review explores the homeostatic disruption of TF-MPs, as the main reservoir of bloodborne TF, in the context of cancer and inflammation, and considers the abrogated responses of the activated endothelium and mononuclear phagocyte system in mediating this disruption

Surface Adsorption Properties of Peptides Produced by Non-optimum pH Pepsinolysis of Proteins: A Combined Experimental and Self-Consistent-Field Calculation Study

Hypothesis Partial hydrolysis of large molecular weight (Mw), highly aggregated plant proteins is frequently used to improve their solubility. However, if this hydrolysis is extensive, random or nonselective, it is unlikely to improve functional properties such as surface activity, emulsion, or foam-stabilising capacity. Experiments and simulation Soy protein isolate (SPI) was hydrolysed by pepsin under optimal (pH 2.1) and non-optimal (pH 4.7) conditions. The surface activity and emulsion stabilising capacity of the resultant peptides were measured and compared. The colloidal interactions between a pair of emulsion droplets were modelled via Self-Consistent-Field Calculations (SCFC). Findings Hydrolysis at pH 2.1 and 4.7 resulted in a considerable increase in measured surface activity compared to the native (non-hydrolysed) SPI, but the hydrolysate from pH 2.1 was not as good an emulsion stabiliser as the hydrolysate (particularly the fraction Mw > 10 kDa) at pH 4.7. Furthermore, peptide analysis of the latter suggested it was dominated by a fragment of one of the major soy proteins β-conglycinin, with Mw ≈ 25 kDa. SCFC calculations confirmed that interactions mediated by adsorbed layers of this peptide point to it being an excellent emulsion stabiliser

Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

Although the association between cancer and venous thromboembolism (VTE) has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n = 9). Within the infarction area of AMI patients (n = 73), this DPP4 expression and activity were significantly decreased, coinciding with an increase in Tissue Factor expression. In primary human umbilical vein endothelial cells (HUVECs), Western blot analysis and digital imaging fluorescence microscopy revealed that DPP4 expression was strongly decreased after metabolic inhibition, also coinciding with Tissue Factor upregulation. Interestingly, inhibition of DPP4 activity with diprotin A also enhanced the amount of Tissue Factor encountered and induced the adherence of platelets under flow conditions. Ischemia induces loss of coronary microvascular endothelial DPP4 expression and increased Tissue Factor expression in AMI as well as in vitro in HUVECs. Our data suggest that the loss of DPP4 activity affects the anti-thrombogenic nature of the endothelium

Soy protein–gum karaya conjugate: emulsifying activity and rheological behavior in aqueous system and oil in water emulsion

The main objective of this study is to investigate the effects of mixing and conjugation of soy protein isolate (SPI) with gum karaya on the characteristics of the hybrid polymer (protein–gum) in both aqueous systems and oil-in-water (O/W) emulsions. It was hypothesized that the covalent linkage of gum karaya with SPI would improve the emulsifying activity and rheological properties of both polymers. Conjugation occurred under controlled conditions (i.e., 60 °C and 75 % relative humidity, 3 days). The conjugated hybrid polymer produced smaller droplet with better uniformity, higher viscosity and stronger emulsifying activity than native gum karaya, suggesting the conjugated polymer provided a bulkier secondary layer with more efficient coverage around oil droplets, thereby inducing stronger resistance against droplet aggregation and flocculation. Emulsions containing the native gum karaya produced the largest droplet size among all prepared emulsions (D 3,2 = 8.6 μm; D 4,3 = 22.4 μm); while the emulsion containing protein–gum conjugate (1:1 g/g) had the smallest droplet size (D 3,2 = 0.2 μm; D 4,3 = 0.7 μm) with lower polydispersity. The protein–gum conjugate (1:1 g/g) also showed the highest elastic and viscous modulus, the lowest polydispersity (span) and the highest emulsifying activity among all native, mixed and conjugated polymers. Therefore, the percentage of gum karaya used for production of O/W emulsion can be decreased by partially replacing it with the conjugated gum