Alterations in fibrin formation and fibrinolysis in early onset-preeclampsia: Association with disease severity.

Objective: ; Early-onset preeclampsia is a rare pregnancy-specific disorder associated with significantly increased maternal and fetal morbidity and mortality. Whilst it is known that even normotensive pregnancies are associated with changes in clot formation and dissolution, the nature of how these changes differ in those with early onset preeclampsia has not been well established. We sought to evaluate parameters of fibrin formation and fibrinolysis in individuals with early onset preeclampsia in comparison to both pregnant and non-pregnant controls.

Computational and experimental analysis of bioactive peptide linear motifs in the integrin adhesome.

Therapeutic modulation of protein interactions is challenging, but short linear motifs (SLiMs) represent potential targets. Focal adhesions play a central role in adhesion by linking cells to the extracellular matrix. Integrins are central to this process, and many other intracellular proteins are components of the integrin adhesome.

The Platelet Releasate is Altered in Human Pregnancy.

Purpose: Healthy pregnancy is characterized by an increase in platelet activation and a decrease in the number of circulating platelets with gestation. Despite this recognized importance, proteomic studies investigating platelets in healthy pregnancy have not been performed. As platelet cargo can be altered in different conditions, it is hypothesized that platelets may store a relevant and bespoke collection of molecules during pregnancy.

Endothelial barrier protective properties of low molecular weight heparin: A novel potential tool in the prevention of cancer metastasis?

Background: One of the key events in the progression of cancer metastasis is the trans-endothelial migration of circulating tumor cells. Moreover, inhibition of tumor-induced vascular permeability has been shown to inhibit metastasis in vivo. Low molecular weight heparin (LMWH) appears to confer a survival benefit in cancer but the underlying mechanisms are poorly understood.

Platelet Releasate Proteome Profiling Reveals a Core Set of Proteins with Low Variance between Healthy Adults.

Upon activation, platelets release a powerful cocktail of soluble and vesicular signals, collectively termed the "platelet releasate" (PR). Although several studies have used qualitative/quantitative proteomic approaches to characterize PR; with debated content and significant inter-individual variability reported, confident, and reliable insights have been hindered. Using label-free quantitative (LFQ)-proteomics analysis, a reproducible, quantifiable investigation of the 1U mL thrombin-induced PR from 32 healthy adults was conducted.

Thrombin generation correlates with disease duration in multiple sclerosis (MS): Novel insights into the MS-associated prothrombotic state.

Background: Thrombin is well recognised for its role in the coagulation cascade but it also plays a role in inflammation, with enhanced thrombin generation observed in several inflammatory disorders. Although patients with multiple sclerosis (MS) have a higher incidence of thrombotic disease, thrombin generation has not been studied to date.

Objectives: The aim of this study was to characterise calibrated automated thrombography parameters in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) in comparison to healthy controls (HCs).

Elevated plasma TFPI activity causes attenuated TF-dependent thrombin generation in early onset preeclampsia.

Early onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin.

Effect of platelet-derived β-thromboglobulins on coagulation.

Background: β-thromboglobulins are derived from the cleavage of the CXC chemokine platelet basic protein and are released in high concentrations by activated platelets. Platelet-derived β-thromboglobulins (βTG) share 70% homology with platelet factor 4 (PF4), another CXC chemokine released by activated platelets. PF4 modulates coagulation by inhibiting heparin-antithrombin interactions, promoting protein C activation, and attenuating the activity of activated protein C.

Cell Adhesion Molecules: Therapeutic Targets for Inhibition of Inflammatory States.

The diversity of integrins and their complex role in many diseases suggests great potential for this superfamily as drug targets. The initial successes of anti-integrin therapeutics in the treatment of thrombotic disorders suggested that similar anti-integrin agents could be developed for the treatment of inflammatory disorders. While initially a promising strategy, inhibition of the integrins proved to be elusive despite the discovery of highly potent inhibitors.

Pregnancy-specific glycoproteins bind integrin αIIbβ3 and inhibit the platelet-fibrinogen interaction.

Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members encoded by multigene families in rodents and primates. In human pregnancy, PSGs are secreted by the syncytiotrophoblast, a fetal tissue, and reach a concentration of up to 400 ug/ml in the maternal bloodstream at term. Human and mouse PSGs induce release of anti-inflammatory cytokines such as IL-10 and TGFβ1 from monocytes, macrophages, and other cell types, suggesting an immunoregulatory function.