A5103248797- Antiplatelet Therapy and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Blood properties and coagulation
- Venous Thromboembolism Diagnosis and Management
- COVID-19 Clinical Research Studies
- Liver Disease Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Atrial Fibrillation Management and Outcomes
- Nitric Oxide and Endothelin Effects
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pharmacology and Obesity Treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diabetes Treatment and Management
- Synthesis of β-Lactam Compounds
- Cholesterol and Lipid Metabolism
- Phagocytosis and Immune Regulation
- Aortic Disease and Treatment Approaches
- Phosphodiesterase function and regulation
- Acute Myocardial Infarction Research
- Endoplasmic Reticulum Stress and Disease
- Eicosanoids and Hypertension Pharmacology
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hormonal and reproductive studies
- Ovarian function and disorders
University of Leeds
2020-2024
RWTH Aachen University
2018
Universitätsklinikum Aachen
2018
Hull York Medical School
2010-2017
University of Hull
2010-2017
Castle Hill Hospital
2010-2011
University of Bradford
2004
University College London
1996-1998
The Royal Free Hospital
1996-1998
Fibrinogen is essential for blood coagulation. The C-terminus of the fibrinogen α-chain (αC-region) composed an αC-domain and αC-connector. Two recombinant variants (α390 α220) were produced to investigate role subregions in modulating clot stability resistance lysis. α390 variant, truncated before αC-domain, clots with a denser structure thinner fibres. In contrast, α220 at start αC-connector, that porous short, stunted fibres visible fibre ends. These mechanically weak susceptible Our data...
The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments we sought understand the structural and mechanical properties blood clots how this influences embolism in vivo. We developed murine model fibrin γ-chain cross-linking by activated...
Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged suggest that thrombi are dynamic structures with distinct areas of differing activation. It was hypothesised PGI2 could reverse spreading by actin cytoskeletal modulation, leading reduced capability aggregates withstand a high shear environment. Our data demonstrates post-flow over activated and spread platelets on fibrinogen, identified significant reduction in surface area under shear....
Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play key role in atherothrombotic process through release inflammatory mediators and formation thrombi. In healthy vessels, excessive platelet activation restricted by endothelial-derived prostacyclin (PGI2) cyclic adenosine-5'-monophosphate (cAMP) protein kinase A (PKA)-dependent mechanisms. Elevation intracellular cAMP associated with control number...
Low-density lipoproteins (LDL) have been various reported to induce platelet aggregation independently and/or sensitise platelets other agonists. In these earlier studies the extent of oxidation LDL was not always or addressed. We now investigated effects native, minimally modified and fully oxidised (0–1gapolipoproteinB100/l on function using aggregometry fluorescence activated flow cytometry.Native did activate isolated but inhibited ADP- thrombin-induced by 51 % in presence absence added...
Abstract Background and Purpose Ticagrelor is labelled as a reversible, direct‐acting platelet P2Y 12 receptor (P2Y R) antagonist that indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As many antiplatelet drugs, ticagrelor therapy increases bleeding risk patients, which may require transfusion emergency situations. The aim this study was to further examine reversibility at R. Experimental Approach Studies were performed human...
Factor III (thromboplastin) activity is inhibited by apoB-100, but the mechanism of inhibition unknown. By examining effect purified apoB-100 on factor activity, we showed that can inhibit via a different from caused issue-factor pathway-inhibitor, which mainly carried surface lipoproteins. Although presence calcium ions and factors X VII may enhance rate inhibition, they are not prerequisite for apoB-100. In addition, investigating changes in UV spectra interaction with assigning shifts...
Vascular inflammation is implicated in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), thought to involve reactive species such as nitric oxide-derived oxidant peroxynitrite. In present study nitrotyrosine was measured a stable marker peroxynitrite production vivo.Perioperative blood samples were obtained from patients undergoing elective open or endovascular repair an AAA with intermittent claudication, smoking aged-matched controls, non-smoking controls young...
Abstract Background The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes and the best dosing regimen remains unclear. This work investigated aspirin dose interaction with glycaemia both cellular protein components thrombosis. Methods A total 48 participants type 1 healthy controls were randomised receive 75 or 300 mg once-daily (OD) an open-label crossover study. Light...
Peroxynitrite, a reactive oxidising species resulting from reaction between nitric oxide and the superoxide anion, modifies proteins by nitration of certain amino acids such as tyrosine. Tissue factor (TF), transmembrane protein, is expressed on cells under inflammatory conditions initiates coagulation cascade. The extracellular domain TF rich in Exposure recombinant cellular to peroxynitrite was associated with reduction procoagulant activity. This accompanied an elevated level...
Abstract Background Infectious diseases are a major cause of mortality in spite existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates infection then apply Mendelian randomisation (MR) yield biomarkers that may be causally associated. Methods used UK Biobank data associate 2,923 proteins with before 31 st December 2019 (240 events 52,520 participants). Since many also predict non-infection mortality, we focussed on those associated...
Granule secretion is an essential platelet function that contributes not only to haemostasis but also wound healing, inflammation, and atherosclerosis. from platelets facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein a protein known modulate the assembly of SNARE complex other cells, its role remains poorly understood. In this study, we provide evidence critical for using...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Introduction Endogenous endothelial vasodilators and ticagrelor both vasodilate inhibit platelets. This study evaluated a potential mechanistic interaction between in patients with stable coronary disease. Methods Participants were assessed at baseline after 3 days of ticagrelor. Blood samples incubated nitric oxide (GSNO) donor or prostacyclin (PGI2) then maximally activated. Using flow cytometry, P-selectin, VASP phosphorylation (-P) platelet leukocyte aggregate (PLA) associated...