A5062376099- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pregnancy and preeclampsia studies
- Redox biology and oxidative stress
- Cardiac Fibrosis and Remodeling
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- S100 Proteins and Annexins
- Cardiac Ischemia and Reperfusion
- Birth, Development, and Health
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Pluripotent Stem Cells Research
- Renin-Angiotensin System Studies
- Cancer, Hypoxia, and Metabolism
- Glutathione Transferases and Polymorphisms
- Eicosanoids and Hypertension Pharmacology
- Reproductive System and Pregnancy
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Eosinophilic Disorders and Syndromes
- Blood Coagulation and Thrombosis Mechanisms
University of Dundee
2018-2024
University of St Andrews
2024
Ninewells Hospital
2021-2024
Genomics (United Kingdom)
2024
King's College London
2007-2021
British Heart Foundation
2009-2021
Boston University
2013-2019
University of Vermont
2019
University of Pretoria
2019
South African Medical Research Council
2019
Objective— Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) a ROS-generating enzyme expressed endothelium, levels which increase pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H 2 O ), but its role vivo remains unclear. Methods and Results— We generated transgenic mice with endothelium-targeted Nox4 overexpression (Tg) to study Nox4. Tg demonstrated...
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms expressed the vessel wall, among which Nox2 is especially abundant endothelium. Endothelial levels rise during but little about cell-specific role of vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression (Tg) studied effects on function blood pressure. Tg had an twofold...
Reactive oxygen species (ROS) are increased in ischemic tissues and necessary for revascularization; however, the mechanism remains unclear. Exposure of cysteine residues to ROS presence glutathione (GSH) generates GSH-protein adducts that specifically reversed by cytosolic thioltransferase, glutaredoxin-1 (Glrx). Here, we show a key angiogenic transcriptional factor hypoxia-inducible (HIF)-1α is stabilized GSH adducts, genetic deletion Glrx improves revascularization. In mouse muscle C2C12...
Abstract Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role multi-functional enzyme Transglutaminase 2 (TG2) cardiac and assess its potential as a therapeutic target. Here describe use highly selective TG2 small-molecule inhibitor to test efficacy inhibition an anti-fibrotic therapy for failure employing two different vivo models fibrosis: Progressively induced interstitial by pressure overload using...
Pathologies associated with uteroplacental hypoxia, such as preeclampsia are among the leading causes of maternal and perinatal morbidity in world. Its fundamental mechanisms yet poorly understood due to a lack good experimental models. Here we report an vitro model placental barrier, based on co-culture trophoblasts endothelial cells against collagen extracellular matrix microfluidic platform. The yields functional syncytium barrier properties, polarization, secretion relevant membrane...
1. Dilatation of the cerebral vasculature is recognised to be involved in pathophysiology migraine. Furthermore, elevated levels prostaglandin E(2) (PGE(2)) occur blood, plasma and saliva migraineurs during an attack, suggestive a contributory role. In present study, we have characterised prostanoid receptors relaxation contraction human middle arteries vitro. 2. presence indomethacin (3 microm) TP receptor antagonist GR32191 (1 microM), PGE(2) was found relax phenylephrine precontracted...
Glutaredoxin-1 (Glrx) is a cytosolic enzyme that regulates diverse cellular function by removal of GSH adducts from S-glutathionylated proteins including signaling molecules and transcription factors. Glrx up-regulated during inflammation diabetes, overexpression inhibits VEGF-induced EC migration. The aim was to investigate the role in angiogenic capacities vivo revascularization setting hind limb ischemia. Glrx-overexpressing transgenic (TG) mice showed impaired migration network formation...
Background: Hypertension caused by increased renin-angiotensin system activation is associated with elevated reactive oxygen species production. Previous studies implicate NADPH oxidase (Nox) proteins as important sources during activation, different Nox isoforms being potentially involved. Among these, Nox2 expressed in multiple cell types, including endothelial cells, fibroblasts, immune and microglia. Blood pressure (BP) regulated at the central nervous system, renal, vascular levels, but...
BackgroundIncreased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) a major ROS source within its activity increases MI. Furthermore, genetic deletion Nox2 protective against post-MI remodeling. levels may increase both cardiomyocytes endothelial cells recent studies indicate cell-specific effects Nox2, but it not known which these cell types important...
Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has high rate morbidity. Therapeutic angiogenesis would re-establish blood perfusion rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces can potentially be used to treat diseases, yet in clinical trials VEGF not fulfilled its full potential with side effects. Whether amino acids promote the molecular mechanisms are largely unknown. Here we showed that (1) Glycine...
Our previous studies showed that the direct injection of an adenovirus construct expressing urokinase-type plasminogen activator (uPA) into experimental venous thrombi significantly reduces thrombus weight. The systemic use vectors is limited by inherent hepatic tropism and inflammatory response. As macrophages are recruited thrombi, it reasonable to speculate these cells could be used target uPA (ad-uPA) gene thrombus. aims this study were determine whether transduced with ad-uPA have...
Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPARgamma) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPARgamma may prevent cardiac fibrosis hypertrophy, recent has suggested pharmacological causes increased mortality. In this study, we investigated effects...
Endothelial activation and inflammatory cell infiltration have important roles in the development of cardiac fibrosis induced by renin-angiotensin system activation. NADPH oxidases (Nox proteins) are expressed endothelial cells (ECs) alter their function. Previous studies indicated that Nox2 ECs contributes to angiotensin II (AngII)-induced fibrosis. However, effects EC Nox4 on unknown. Transgenic (TG) mice overexpressing endothelial-restricted were studied alongside wild-type (WT)...