A5026980755- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Erythropoietin and Anemia Treatment
- Trace Elements in Health
- Pregnancy and preeclampsia studies
- Congenital Heart Disease Studies
- Cardiovascular Issues in Pregnancy
- Congenital heart defects research
- Cardiac Structural Anomalies and Repair
- Cardiovascular Function and Risk Factors
- MicroRNA in disease regulation
- Pulmonary Hypertension Research and Treatments
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Fuel Cells and Related Materials
- Heart Failure Treatment and Management
- Ion channel regulation and function
- Biomedical Text Mining and Ontologies
- Cancer-related molecular mechanisms research
- Child Nutrition and Water Access
- Neuroendocrine Tumor Research Advances
- Folate and B Vitamins Research
- Extracellular vesicles in disease
University of Oxford
2016-2025
Significance The iron-exporting protein ferroportin is recognized as central to systemic iron regulation, but its role in tissues other than those involved handling unknown. This study shows that expression cardiomyocytes essential intracellular homeostasis and normal cardiac function. It also demonstrates the site of accumulation iron-overloaded heart depends on whether expressed cardiomyocytes. further functional significance overload highly dependent upon accumulation. These findings...
Iron-related disorders are among the most prevalent diseases worldwide. Systemic iron homeostasis requires hepcidin, a liver-derived hormone that controls mobilization through its molecular target ferroportin (FPN), only known mammalian exporter. This pathway is perturbed in cause overload. Additionally, intestinal HIF-2α essential for local absorptive response to systemic deficiency and Our data demonstrate hetero-tissue crosstalk mechanism, whereby hepatic hepcidin regulated deficiency,...
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from liver, it inhibits exporter ferroportin in gut and spleen, sites absorption recycling respectively. Recently, we demonstrated that also found cardiomyocytes, its cardiac-specific deletion leads to fatal cardiac overload. expressed where function remains unknown. To define cardiomyocyte hepcidin, generated mice with cardiomyocyte-specific or knock-in hepcidin-resistant ferroportin. We find while both models...
Ironing out the details of mucosal healing Anemia is a frequent complication disorders such as inflammatory bowel disease, occurring in part result increased bleeding into intestine. Bessman et al. show that peptide hormone hepcidin, which regulates systemic iron homeostasis, required for intestinal repair mouse model disease (see Perspective by Rescigno). This effect was independent hepatocyte-produced hepcidin and levels. Instead, production conventional dendritic cells necessary...
Abstract Background and Aims Intravenous iron therapies contain iron–carbohydrate complexes, designed to ensure becomes bioavailable via the intermediary of spleen liver reticuloendothelial macrophages. How other tissues obtain handle this remains unknown. This study addresses question in context heart. Methods A prospective observational was conducted 12 patients receiving ferric carboxymaltose (FCM) for deficiency. Myocardial, spleen, magnetic resonance relaxation times plasma markers were...
Significance Pulmonary arterial hypertension (PAH) is a disease in which lung blood pressure raised chronically, causing right heart failure. It has been shown that iron deficiency also raises pressure. However, we don’t know the mechanisms because understand precisely how cells of vessels are affected by levels. The smooth muscle important for controlling Our study shows specifically within these sufficient to cause PAH, even against background normal levels other tissues.
Iron deficiency is present in ~50% of heart failure (HF) patients. Large multicenter trials have shown that treatment iron with i.v. benefits HF patients, but the underlying mechanisms are not known. To investigate actions on heart, mice were fed an iron-depleted diet, and some received ferric carboxymaltose (FCM), supplementation used clinically. Iron-deficient animals became anemic had reduced ventricular ejection fraction measured by magnetic resonance imaging. Ca2+ signaling, a pathway...
Abstract Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence 0.9% births. However, two-thirds cases have an unknown cause, and many these are thought to be caused by in utero exposure environmental teratogens. Here we identify potential teratogen causing CHD mice: maternal iron deficiency (ID). We show that ID mice causes severe cardiovascular defects offspring. These likely arise from increased retinoic acid signalling embryos. The can prevented...
Aims Iron deficiency (ID) is a common co-morbidity in heart failure (HF). Intravenous iron therapy improves outcomes. Several mechanisms have been proposed, including myocardial repletion. However, it unknown if clinical markers predict the extent of this The aim study to address question by harnessing data from two studies that evaluated changes using cardiac magnetic resonance (CMR). Methods and Results We performed post-hoc analysis previously published trials. Myocardial-IRON trial...
ABSTRACT Background and aims Iron deficiency (ID) is common in patients with acute STEMI. ID has previously been associated either adverse or favourable effects, depending on the definition of ID, sampling timepoint, outcome measures follow-up duration. This study systematically addresses impact long-term outcomes explores underlying mechanisms. Methods Patients STEMI (n=167) were followed for 4.5 years major cardiovascular events (MACE), including new HF diagnosis, recurrent MI cardiac...
Hepcidin levels are high and iron absorption is limited in acute malaria. The mechanism(s) that regulate hepcidin secretion remain undefined. We have measured concentration cytokines 100 Kenyan children with falciparum malaria different degrees of anemia. was increased on admission fell significantly one week month after treatment. association hemoglobin not linear very low severe malarial Parasite density, IL-10 IL-6 were associated concentration. response to supports the notion...
The hepcidin/ferroportin axis controls systemic iron homeostasis by regulating acquisition from the duodenum and reticuloendothelial system, respective sites of absorption recycling. Ferroportin is also abundant in kidney, where it has been implicated tubular reabsorption. However, remains unknown whether endogenous hepcidin regulates ferroportin-mediated reabsorption under physiological conditions, such regulation important for kidney and/or homeostasis. To address these questions, we...
Iron deficiency is the most prevalent micronutrient disorder globally. When severe, iron leads to anemia, which can be deleterious cardiac function. Given central role of and oxygen in biology, multiple pathways are expected altered iron-deficiency identifying these requires an unbiased approach. To investigate changes, gene expression metabolism were studied mice weaned onto iron-deficient diet for 6 weeks. Whole-exome transcriptomics (RNAseq) identified over 1,500 differentially expressed...
Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient invading pathogens, impairing their growth. Hepcidin (Hamp1) the master regulator and its expression induced by inflammation. Mice lacking Hamp1 birth rapidly accumulate are susceptible to infection blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order study role hepcidin against background normal status, we developed transgenic mouse...
Hepcidin is a liver-derived hormone that controls systemic iron homeostasis, by inhibiting the exporter ferroportin in gut and spleen, respective sites of absorption recycling. also expressed ectopically context cardiovascular disease. However, precise role ectopic hepcidin underlying pathophysiology unknown. In patients with abdominal aortic aneurysm (AAA), markedly induced smooth muscle cells (SMCs) wall inversely correlated expression LCN2 (lipocalin-2), protein implicated AAA pathology....