A5056729650- Blood Coagulation and Thrombosis Mechanisms
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protease and Inhibitor Mechanisms
- Lipoproteins and Cardiovascular Health
- Cell Adhesion Molecules Research
- Sphingolipid Metabolism and Signaling
- Platelet Disorders and Treatments
- Phagocytosis and Immune Regulation
- Pancreatitis Pathology and Treatment
- Venomous Animal Envenomation and Studies
- Antiplatelet Therapy and Cardiovascular Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Venous Thromboembolism Diagnosis and Management
- Calpain Protease Function and Regulation
- Lysosomal Storage Disorders Research
- Vitamin K Research Studies
- Proteoglycans and glycosaminoglycans research
- Complement system in diseases
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Apelin-related biomedical research
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
- Cancer, Lipids, and Metabolism
- Retinoids in leukemia and cellular processes
Hammersmith Hospital
2011-2025
Imperial College London
2016-2025
Imperial College Healthcare NHS Trust
2019
Lund University
2007-2015
Skåne University Hospital
2011
Wallenberg Wood Science Center
2008
Uppsala University
2004
Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated ApoM(+) HDL contained S1P, whereas ApoM(-) did not. Moreover, in Apom(-/-) mice contains no transgenic overexpressing apoM has an increased content. The 1.7-Å structure S1P-human complex reveals interacts with amphiphilic pocket lipocalin fold apoM. Human...
Summary. The primary aim of this study was to investigate the possible relationship between coagulation factor level and bleeding frequency during prophylactic treatment haemophilia after stratification patients according joint scores. secondary obtain a systematic overview doses factors prescribed for prophylaxis at Malmö centre 6‐year period. A retrospective survey medical records years 1997–2002 pharmacokinetic results from 1990s complemented by collection blood samples assay when needed....
Apolipoprotein M (apoM) is a 188 amino acid, 25 kDa protein belonging to the lipocalin superfamily. Although predominantly associated with high density lipoprotein, apoM found in all major lipoprotein classes. To facilitate clinical studies of apoM, we have developed sandwich ELISA for measurement human plasma. This method has been used investigate normal variation and establish reference values healthy individuals through 598 samples from Nordic Reference Interval Project Bio-bank Database...
Kallikrein (PKa), generated by activation of its precursor prekallikrein (PK), plays a role in the contact phase coagulation and functions kallikrein-kinin system to generate bradykinin. The general dogma has been that contribution PKa cascade is dependent on action FXII. Recently this challenged studies human plasma showing thrombin generation due activity FIX also murine formation FIXa-antithrombin complexes FXI deficient mice. In study, we demonstrate high-affinity binding interactions...
Hemorrhage is the leading cause of trauma death, and innovation in hemostatic technology important. The strongly hydrophobic carbon nanofiber (CNF) coating has previously been shown to have excellent properties. However, understanding how CNF guides coagulation cascade biosafety as agents yet be explored. Here, our thrombin generation assay investigation showed that induced fast blood via factor (F) XII activation intrinsic pathway. We further performed studies a rat vein injury demonstrated...
A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since underlying mechanism not known, we have investigated effect mycolactone on endothelial cells, focussing expression surface anticoagulant molecules involved protein C pathway. Congenital deficiencies this natural pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis....
Apolipoprotein M (apoM) is a plasma protein associated mainly with HDL. ApoM suggested to be important for the formation of preβ-HDL, but its mechanism action unknown. Homology modeling has apoM lipocalin. Lipocalins share structurally conserved β-barrel, which in many lipocalins bind hydrophobic ligands. The aim this study was test ability different substances. produced both Escherichia coli and HEK 293 cells. Characterization variants electrophoretic immunological methods from E. correctly...
Tissue factor pathway inhibitor (TFPI), the main of initiation coagulation, exerts an important anticoagulant role through Xa (FXa)-dependent inhibition tissue factor/factor VIIa. Protein S is a TFPI cofactor, enhancing efficiency FXa inhibition. can also inhibit prothrombinase assembly by directly interacting with coagulation V (FV), which has been activated FXa. Because full-length associates FV in plasma, we hypothesized that may influence inhibitory function. Using pure component assays,...
Abstract Platelet-derived extracellular vesicles (PDEVs) are the most abundant amongst all types of EVs in circulation. However, mechanisms leading to PDEVs release, their role coagulation and phenotypic composition poorly understood. from washed platelets were generated using different stimuli characterised nanoparticle tracking analysis. Procoagulant properties evaluated by fluorescence flow cytometry calibrated automated thrombography. plasma isolated concentrated a novel protocol...
Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin family, is predominantly associated with HDL. Studies in mice have suggested apoM be important for formation of pre-beta-HDL and increase cholesterol efflux from macrophage foam cells. Overexpression human LDL receptor-deficient reduced atherogenic effect cholesterol-rich diet. The aim present study was investigate whether levels man predict risk coronary heart disease (CHD). ApoM measured samples two separate...
Apolipoprotein M (apoM) is predominantly associated with HDL. In this study, it was investigated whether apoM's uncleaved signal peptide necessary for the protein's ability to associate lipoproteins. ApoM a cleavable peptide, Q22A, expressed, together wild‐type apoM, in HEK293 cells. On size‐exclusion chromatography, elution profile of apoM similar that human HDL‐associated plasma apoM. contrast, size Q22A mutant corresponded free, unassociated This strongly indicates indeed lipid.
Abstract Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential endothelial homeostasis. Here, we show that inducible deletion ( Erg iEC-KO ) in mice associated with spontaneous thrombosis, hemorrhages We find drives the anticoagulant thrombomodulin (TM), as shown by reporter assays chromatin immunoprecipitation. TM expression regulated shear stress (SS)...
Abstract ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 -5 share the abilities to cleave large aggregating proteoglycans including versican aggrecan. These activities are highly relevant cardiovascular disease osteoarthritis during development. Here, using purified recombinant ADAMTS-1, -5, we quantify, compare, define molecular basis of their versicanase activity. A novel sandwich-ELISA detecting major cleavage fragment was used determine,...
Deep vein thrombosis is a major cause of morbidity and mortality worldwide. However, because the absence overt blood vessel damage, how venous actually initiated remains unclear. Using endothelialized fluidic devices, we show that aberrant flow patterns may occur in valve pockets individuals with common stasis-related risk factors can formation von Willebrand factor–platelet tangles are resistant to ADAMTS13 removal. These factor–bound platelets specifically recruit neutrophils manner...
A disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs (ADAMTS)8 is a secreted protease, which was recently implicated in pathogenesis of pulmonary arterial hypertension (PAH). However, the substrate repertoire ADAMTS8 regulation its activity are incompletely understood. Although considered proteoglycanase because high sequence similarity close phylogenetic relationship to proteoglycan-degrading proteases ADAMTS1, 4, 5, 15, as well tight genetic linkage ADAMTS15 on...