A5084082130- Hormonal Regulation and Hypertension
- Angiogenesis and VEGF in Cancer
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Nitric Oxide and Endothelin Effects
- Hormonal and reproductive studies
- Air Quality and Health Impacts
- Eicosanoids and Hypertension Pharmacology
- Estrogen and related hormone effects
- Apelin-related biomedical research
- Energy and Environment Impacts
- Adrenal Hormones and Disorders
- Liver Disease and Transplantation
- Birth, Development, and Health
- Cardiovascular Disease and Adiposity
- Energy, Environment, and Transportation Policies
- Adipose Tissue and Metabolism
- Pregnancy and preeclampsia studies
- Cardiac Fibrosis and Remodeling
- Coronary Interventions and Diagnostics
- Climate Change and Health Impacts
- Renin-Angiotensin System Studies
- Liver Disease Diagnosis and Treatment
- Protease and Inhibitor Mechanisms
- Sperm and Testicular Function
- Adrenal and Paraganglionic Tumors
University of Edinburgh
2016-2025
The Queen's Medical Research Institute
2013-2023
British Heart Foundation
2011-2021
MRC Centre for Reproductive Health
2010-2016
University of Basel
2016
Skolkovo Institute of Science and Technology
2016
Addenbrooke's Hospital
2016
Medical Research Council
2016
British Heart Foundation Centre for Cardiovascular Science
2013
Aston University
2013
The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. mechanisms through which inhalation could trigger acute cardiovascular events emerging, but a fundamental unanswered question remains: Do inhaled translocate from the lung in man directly contribute pathogenesis disease? In complementary clinical experimental...
The exact etiology of preeclampsia is unknown, but there growing evidence an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), proangiogenic vasodilator. We hypothesized that reduction CSE activity may alter the balance pregnancy induce placentation maternal hypertension.Plasma levels H2S were significantly decreased women with (P<0.01), which was associated reduced placental...
AimExposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess role combustion-derived-nanoparticles in mediating adverse cardiovascular effects pollution.
A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order harness their potential for cardiovascular regeneration. Endothelial outgrowth (EOC) most closely fulfil the criteria an EPC, but origin remains obscure. Our aim was source and precursor EOC assess regenerative compared mature cells. are readily isolated from umbilical cord blood (6/6 donors) peripheral mononuclear (4/6 not bone marrow (0/6) or following mobilization with granulocyte-colony...
Diesel exhaust particulate (DEP), a major component of urban air pollution, has been linked to atherogenesis and precipitation myocardial infarction. We hypothesized that DEP exposure would increase destabilise atherosclerotic lesions in apolipoprotein E deficient (ApoE−/−) mice. ApoE−/− mice were fed 'Western diet' (8 weeks) induce 'complex' plaques, with parallel experiments normal chow wild-type During the last 4 weeks feeding, received twice weekly instillation (oropharyngeal aspiration)...
Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution.We carried out RNA sequencing (scRNA-seq) lung ECs isolated from an lineage-tracing mouse model Control SU5416/hypoxia-induced conditions. populations corresponding distinct vessel types, including two discrete capillary populations, were identified both mice. Differential gene expression analysis revealed...
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Diesel exhaust particulate (DEP) is a key arbiter of the adverse cardiovascular effects air pollution.We assessed in vitro DEP on vascular function, nitric oxide (NO) availability, and generation oxygen-centered free radicals.We direct (10-100 microg/mL) isolated rat aortic rings using myography. We investigated NO scavenging radical an electrode electron paramagnetic resonance (EPR) with Tempone-H (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) spin trap,...
Background Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth new blood vessels have not been established. This study addresses hypothesis that physiological levels by directly preventing tube formation endothelial cells. Methodology/Principal Findings Cultured human umbilical vein (HUVEC) aortic (HAoEC) cells were used to determine influence on tube-like structure...
MicroRNAs (miRNAs) directly regulate gene expression at a post-transcriptional level and represent an attractive therapeutic target for wide range of diseases. Here, we report novel strategy delivering miRNAs to endothelial cells (ECs) angiogenesis, using polymer functionalized carbon nanotubes (CNTs). CNTs were coated with two different polymers, polyethyleneimine (PEI) or polyamidoamine dendrimer (PAMAM), followed by conjugation miR-503 oligonucleotides as recognized regulators...
Key points Glucocorticoids are known to be present in the developing zebrafish embryo but little is about their physiological role at this early stage. The demonstrates a functional glucocorticoid system from around 48 h post fertilisation. This and stress response amenable pharmacological genetic manipulation manner predicted by mammalian physiology. play key developmental hatching, swimming response. relevant model for study of Abstract While glucocorticoids (GCs) embryo, roles We...
Maternal obesity during pregnancy has been linked to an increased risk of and cardiometabolic disease in the offspring, a phenomenon attributed developmental programming. Programming effects may be transmissible across generations through both maternal paternal inheritance, although mechanisms remain unclear. Using mouse model, we explored moderate diet-induced (DIO) on weight gain glucose-insulin homeostasis first-generation (F1) second-generation offspring. DIO was associated with insulin...
Abstract Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of disease, compared to women similar age. These gender disparities suggest an influence sex hormones. Testosterone is the primary most well-recognised androgen in men. Therefore, we addressed hypothesis that exogenous treatment induces vascular calcification. Immunohistochemical analysis revealed expression receptor (AR) calcified media human femoral artery tissue...
Although the prevalence of obesity is higher among women than men, they are somewhat protected from associated cardiometabolic consequences. The increase in cardiovascular disease risk seen after menopause suggests a role for estrogens. There also growing evidence importance estrogen on body fat and metabolism males. We hypothesized that administration would ameliorate adverse effects metabolic parameters Male female C57Bl/6 mice were fed control or obesogenic (DIO) diets 5 weeks age until...
Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but mechanisms are complex not completely elucidated. The present study was designed investigate hypothesis that activation pulmonary sensory receptors sympathetic nervous system underlies influence diesel exhaust particulate on blood pressure, myocardial response ischemia reperfusion. 6 h after intratracheal instillation (0.5 mg), reperfusion...
The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. is also instrumental to testis function because it both route by which gonadotropins are delivered T transported away target organs. Whether Sertoli cells play role in regulating postnatal life has never been unequivocally demonstrated. In this study we used models of acute cell ablation germ address whether actively influence vascular structure adult Our findings...
In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences activity and fate nanoparticle in vivo. Corona composition is often determined by the milieu encountered at entry portal into body, and, can therefore, depend route exposure to nanoparticle. For environmental where inhalation, this will be lung lining fluid. This study examined plasma bronchoalveolar fluid (BALF) binding engineered nanoparticles. We...
Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodeling. However, the molecular mechanisms that govern this remain largely unknown, including contribution of long noncoding RNAs (lncRNAs). Objectives: To investigate role lncRNAs EndMT and their relevance to Methods Results: study vitro, primary endothelial cells were treated with transforming growth factor-β2 interleukin-1β. Single-cell bulk RNA-seq...
Angiogenesis restores blood flow to healing tissues, a process that is inhibited by high doses of glucocorticoids. However, the role endogenous glucocorticoids and potential for antiglucocorticoid therapy enhance angiogenesis unknown. Using in vitro vivo models mice, we examined effects ( i ) glucocorticoids, ii blocking glucocorticoid action with receptor antagonist RU38486, iii abolishing local regeneration enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). Glucocorticoids,...
Mineralocorticoid receptor (MR) activation is proinflammatory and proatherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, exacerbates atherosclerosis. The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) prevents inappropriate the inactivating glucocorticoids mineralocorticoid-target tissues. To determine whether glucocorticoid-mediated increases atheromatous plaque formation, we generated...