A5090928090- Atherosclerosis and Cardiovascular Diseases
- Pulmonary Hypertension Research and Treatments
- Cell Adhesion Molecules Research
- Coronary Interventions and Diagnostics
- Adipokines, Inflammation, and Metabolic Diseases
- Angiogenesis and VEGF in Cancer
- Endoplasmic Reticulum Stress and Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Parathyroid Disorders and Treatments
- Bone health and treatments
- Cerebrovascular and Carotid Artery Diseases
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- Cardiac and Coronary Surgery Techniques
- Cell death mechanisms and regulation
- Bone Metabolism and Diseases
- Protease and Inhibitor Mechanisms
- MicroRNA in disease regulation
- Acute Myocardial Infarction Research
- Galectins and Cancer Biology
- Immune cells in cancer
- RNA Interference and Gene Delivery
- interferon and immune responses
- Biomarkers in Disease Mechanisms
University of Sheffield
2016-2025
Insigneo
2016-2025
Louisiana State University Health Sciences Center Shreveport
2024
Royal Hallamshire Hospital
2007-2022
University of Michigan
2018
Harvard University
2016
Boston Children's Hospital
2016
Imperial College London
2016
Erasmus University Rotterdam
2016
KU Leuven
2016
We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in cells that metastasise to compared with do not. now investigated the functional role of IL-1 by blocking IL-1R signalling clinically licensed antagonist, anakinra.6-week old female BALB/c mice received subcutaneous or intra-venous injection MDA-MB-231-IV MCF7 cells....
Interleukin-1β (IL-1β ) is known to have a number of effects on the different cell types present within coronary arteries. In this study we identified location and phenotype cells containing IL-1β in human artery specimens from patients suffering either atherosclerosis or cardiomyopathy correlated presence with disease severity. Luminal endothelial cells, adventitial vessel wall macrophages were double labeled immunohistochemically for protein type–specific monoclonal antibody macrophages....
The human malaria parasite, Plasmodium falciparum, de- grades nearly all its host cell hemoglobin during a short seg- ment of intraerythrocytic development.This massive cata- bolic process occurs in an acidic organelle, the digestive vacu- ole.Aspartic and cysteine proteases have been implicated this pathway.We isolated three vacuolar that account for most globin-degrading activity diges- tive vacuole.One is previously described aspartic hemoglo- binase initiates degradation.A second...
Vascular development and maturation are dependent on the interactions of endothelial cell integrins with surrounding extracellular matrix. Previous investigations primacy certain in vascular have not addressed whether this could also be a secondary effect due to poor embryonic nutrition. Here, we show that α 5 integrin subunit fibronectin critical roles blood vessel mouse embryos embryoid bodies (EBs) differentiated from stem cells (a situation which there is no nutritional deficit caused by...
Plasmodium falciparum is the major causative agent of malaria, a disease worldwide importance. Resistance to current drugs such as chloroquine and mefloquine spreading at an alarming rate, our antimalarial armamentarium almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I II, which are essential components its hemoglobin-degradation pathway novel targets for drug development. We have determined crystal structure recombinant plasmepsin II complexed...
Background —Cytokine gene variations are contributory factors in inflammatory pathology. Allele frequencies of interleukin (IL)-1 cluster genes [IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and tissue necrosis factor (TNF)-α [TNFA(-308)] were measured healthy blood donors (healthy control subjects), patients with angiographically normal coronary arteries (patient single-vessel disease (SVD), those multivessel (MVD). Methods Results —Five hundred fifty-six attending for...
Abstract —The proinflammatory cytokine interleukin (IL)-1 is expressed mainly within the endothelium of atherosclerotic plaques and may be linked with inflammatory mechanisms atherogenesis. IL-1 action complex regulated in part by its naturally occurring inhibitor, receptor antagonist (IL-1ra). Therefore, we studied differential specific isoform expression IL-1ra diseased coronary arteries endothelial cells (ECs) stimulated under defined conditions. In view an association gene (IL-1RN)...
Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that inflammation may contribute to the development stroke in humans. The hypothesis induce brain pathology can be tested animals, this was key objective present study. First, we assessed changes rodent models chronic, inflammation. PET imaging revealed microglia activation JCR-LA (corpulent) rats, develop atherosclerosis obesity, compared...
Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying stress-regulation EndMT are uncertain. Here we investigated the role transcription factor Snail in low stress-induced EndMT. Studies cultured exposed to revealed that induced expression. Using gene silencing it was demonstrated...
Loss of the growth-suppressive effects bone morphogenetic protein (BMP) signaling has been demonstrated to promote pulmonary arterial endothelial cell dysfunction and induce smooth muscle (PASMC) proliferation, leading development hypertension (PAH). MicroRNAs (miRs) mediate higher order regulation cellular function through coordinated modulation mRNA targets; however, miR expression is altered by disease drug therapy. Here, we examined treatment-naive patients experimental models PAH...
ABSTRACT Novel therapeutics targeting neutrophilic inflammation are a major unmet clinical need in acute and chronic inflammation. The timely induction of neutrophil apoptosis is critical for resolution, it thought that acceleration may facilitate resolution at inflammatory sites. We previously demonstrated death receptor ligand, TRAIL, accelerates vitro. examined the role TRAIL neutrophil-dominant WT TRAIL-deficient mice. deficiency did not alter constitutive apoptosis, whereas exogenous...
Rationale: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed embryogenesis, but its role in EC responses to and focal unknown. Objective: To investigate whether regulates vascular dysfunction compare function development disease. Methods Results: expression of TWIST1 was studied both developing vasculature the initiation...
Abstract Neutrophils are implicated in the pathogenesis of atherosclerosis but seldom detected atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels circulating neutrophil enhanced by exposure to a high fat diet, known risk factor for atherosclerosis. Neutrophil accumulate at disease-prone regions arteries exposed disturbed flow patterns, and promote vascular inflammation murine model. Using...
Background —Restenosis after percutaneous coronary intervention remains a serious clinical problem. Progress in local gene therapy to prevent restenosis has been hindered by concerns over the safety and efficacy of viral vectors limited efficiency nonviral techniques. This study investigates use adjunctive ultrasound enhance delivery. Methods Results —Cultured porcine vascular smooth muscle cells (VSMCs) endothelial (ECs) were transfected with naked or liposome-complexed luciferase reporter...
Background —Angioplasty initiates a number of responses in the vessel wall including cellular migration, proliferation, and matrix accumulation, all which contribute to neointima formation restenosis. Cellular homeostasis within tissue depends on balance between cell proliferation apoptosis. Methods Results —Profiles apoptosis were therefore examined porcine PTCA injury model over 28-day period. Forty-two arteries from 21 pigs, harvested at site maximal 1, 6, 18 hours, 3, 7, 14, 28 days...
1. A meta-analysis of 17 years literature on erythrocyte Na+/Li+ countertransport (NLCT) and Na+/K+ co-transport (COT) measurements in relation to essential hypertension is presented. The analysis aimed answer two questions: (i) Which clinical or laboratory variables influence NLCT COT flux values? (ii) How useful are as a diagnostic aid hypertension? 2. Regression was performed the mean values relevant values. Studies both normotensive hypertensive subjects were stratified for which showed...
Atherosclerosis is an inflammatory process that develops in individuals with known risk factors include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, mechanisms vascular requires further research. We hypothesised interleukin-1 (IL-1) signaling vessel wall would raise arterial blood pressure promote atheroma.Apoe(-/-) Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, their atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) had...