A5006418746- Nitric Oxide and Endothelin Effects
- Cardiovascular Function and Risk Factors
- Metabolism and Genetic Disorders
- Cholesterol and Lipid Metabolism
- Mitochondrial Function and Pathology
- Cardiac electrophysiology and arrhythmias
- Atrial Fibrillation Management and Outcomes
- Fatty Acid Research and Health
- Folate and B Vitamins Research
- Paraoxonase enzyme and polymorphisms
- Advanced MRI Techniques and Applications
- Diabetes and associated disorders
- Cardiomyopathy and Myosin Studies
- Receptor Mechanisms and Signaling
- Peroxisome Proliferator-Activated Receptors
- Antioxidant Activity and Oxidative Stress
- Adipose Tissue and Metabolism
- Edible Oils Quality and Analysis
- Atherosclerosis and Cardiovascular Diseases
- Renin-Angiotensin System Studies
- Anodic Oxide Films and Nanostructures
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Conducting polymers and applications
- Cardiac Ischemia and Reperfusion
- Immune cells in cancer
University of Oxford
2015-2024
John Radcliffe Hospital
2012-2024
Brunel University of London
2024
British Heart Foundation
2023
Centre for Human Genetics
2018
Ricardo (United Kingdom)
2016
University of Leeds
2013
Universidad de Zaragoza
2003-2010
Instituto Aragonés de Ciencias de la Salud
2008-2010
Gobierno de Aragón
2008-2010
Background: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity macrophages, promoting persistent proatherogenic characteristics. Methods: Bone marrow–derived macrophages from control mice and with were grown physiological glucose (5 mmol/L) subjected to RNA sequencing (n=6), assay for transposase accessible chromatin immunoprecipitation (n=6) determination of hyperglycemia-induced immunity. marrow...
Atrial fibrillation (AF) is a growing public health burden, and its treatment remains challenge. AF leads to electrical remodeling of the atria, which in turn promotes maintenance resistance treatment. Although has long been therapeutic target AF, causes remain poorly understood. We show that atrial-specific up-regulation microRNA-31 (miR-31) goat human depletes neuronal nitric oxide synthase (nNOS) by accelerating mRNA decay alters nNOS subcellular localization repressing dystrophin...
Medium-chain length polyhydroxyalkanoates (MCL-PHAs) have demonstrated exceptional properties for cardiac tissue engineering (CTE) applications. Despite prior work on MCL-PHA/polycaprolactone (PCL) blends, optimal scaffold production and use as an alternative delivery route controlled release of seeded progenitor cells (CPCs) in CTE applications vivo has been lacking. We present herein applicability MCL-PHA/PCL (95/5 wt %) blends fabricated thin films with improved performance compared to...
Hydroxytyrosol is a phenol found in olive oil. To verify the effect of hydroxytyrosol on development atherosclerosis, two groups apo E deficient male mice standard chow diet were used: control group receiving only water, and second an aqueous solution order to provide dose 10 mg/kg/day each mouse. This treatment was maintained for weeks. At moment sacrifice, blood drawn heart removed. Plasma lipids, apolipoproteins monocyte Mac-1 expression assayed as well aortic atherosclerotic areas both...
We assessed the effects of Picual and Arbequina olive oil, rich poor in polyphenols, respectively, on plasma lipid glucose metabolism, hepatic fat content, proteome female Apoe-/- mice. Both oils increased content adipophilin levels (p < 0.05), though oil significantly decreased triglycerides 0.05). Proteomics identified a range antioxidant enzymes that were differentially regulated by both as compared with palm oil. found clear association between consumption differential regulation betaine...
Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOS). Oral BH4 supplementation preserves cardiac function in animal models disease; however, the mechanisms underlying these findings are not completely understood.To study effect myocardial transgenic overexpression rate-limiting enzyme biosynthesis, GTP cyclohydrolase 1 (GCH1), on NOS activity, function, and Ca2+ handling.GCH1overexpression significantly increased biopterins level left ventricular (LV) myocytes...
Background Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzyme's function so it generates superoxide rather than nitric oxide. with chronic pressure overload, and both are ameliorated by exogenous tetrahydrobiopterin ( BH 4)—a cofactor required for normal function—supporting a pathophysiological link. Genetically augmenting 4 synthesis in endothelial cells fails to replicate this benefit, indicating that other cell types dominate effects...
Abstract Aims Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling animal models predicts incident AF humans; however, direct causal role for has not been demonstrated. Accordingly, we investigated whether overexpression mice (NOX2-Tg) is sufficient to generate favourable substrate further assessed the effects atorvastatin, an inhibitor NOX2,...
In human reproduction, hyperhomocysteinemia has been reported as a risk factor for early pregnancy loss and congenital birth defects. Hyperhomocysteinemia is also recognized cause of maternal obstetric complications such preeclampsia. The role plasma in female fertility was examined using cystathionine beta synthase knockout (cbs KO) mice. Cbs KO females were infertile, showed alterations the estrus cycle an increased progesterone response during pseudo-pregnancy induction. Both cbs ovaries...
Abstract Propiogenic substrates and gut bacteria produce propionate, a post-translational protein modifier. In this study, we used mouse model of propionic acidaemia (PA) to study how disturbances propionate metabolism result in histone modifications changes gene expression that affect cardiac function. Plasma surrogates were raised PA mice, but female hearts manifested more profound acyl-CoAs, propionylation acetylation, transcription. These resulted moderate diastolic dysfunction with Ca...
In diabetic patients, heart failure with predominant left ventricular (LV) diastolic dysfunction is a common complication for which there no effective treatment. Oxidation of the NOS (nitric oxide synthase) cofactor tetrahydrobiopterin (BH4) and dysfunctional activity have been implicated in pathogenesis vascular cardiomyopathic phenotype.Using mice models human myocardial samples, we evaluated whether by mechanism increasing BH4 availability prevented or reversed LV induced diabetes.In...
Abstract Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver diabetes‐associated complications, mediated by biological processes such as dysfunction endothelial cells, fibrosis, and alterations in leukocyte number function. Here, we dissected the transcriptional response key cell types to hyperglycemia across tissues using single‐cell RNA sequencing (scRNA‐seq) identified conserved, well organ‐specific, changes associated with...
The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two oils, obtained from same cultivar but by different technological procedures, were characterized to show they differed mainly terms composition/quantity this fraction. Using DNA microarrays, analysed apoE-deficient mice fed one two isoenergetic, isonitrogenous diets containing either 10 % (w/w) or fraction-enriched oil. To provide an initial screening potential...
AimsIn healthy hearts, the neuronal nitric oxide synthase (nNOS) is predominantly localized to sarcoplasmic reticulum (SR), where it regulates ryanodine receptor Ca2+ release channel (RyR2) and phospholamban (PLB) phosphorylation, a lesser extent sarcolemmal membrane inhibits L-type current (ICa). However, in failing impaired relaxation depressed inotropy are associated with larger proportion of nNOS being membrane. Whether there causal relationship between altered myocardial function...
Purpose To a) achieve cardiac 19F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration cellular load limits, c) spectroscopic image-based quantification. Methods Theoretical simulations experimental comparisons spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), steady state at free precession (SSFP) pulse sequences, phantom validations,...