Projects

Projects

Impact of Insulin Pump Therapy and Islet Transplantation on Progression of Diabetic Retinopathy in Type 1 Diabetes

Diabetic retinopathy is a clinically well-defined, sight threatening, chronic microvascular complication that eventually affects virtually all people with diabetes. It represents one of the major causes of blindness in the world. Therapies associated with improvement in hyperglycaemia include insulin pump therapy and islet transplantation. However the impact of such therapies on the progression of diabetic retinopathy have not been well studied particularly in relation to the stabilisation of their glycaemic control. We aim to examine prospectively a cohort of subjects preceding commencement of insulin pump/islet transplantation at regular intervals for 1 year. Such studies will allow robust assessments of the relationship between changes in metabolic control and eye disease, and may inform screening strategies with respect to islet transplantation, therefore leading to improved medical outcomes.  

Utilisation of Novel Contrast Agents in Studies of Type 1 and Type 2 Diabetes

Manganese (Mn2+) is taken up in beta cells of islets via voltage-gated calcium channels. Since both Type 1 and Type 2 diabetes are characterised by diminished numbers and activity of beta cells, non-invasive detection of beta cells with manganese compounds may allow monitoring of treatment or disease progression. The contrast agent manganese gluconate is licensed in man and working with the Clinical Research Imaging Centre, we have demonstrated its utility in a rat model. In these studies, rats were administered 50% dextrose (2ml/kg) and enhancement of the liver was compared to enhancement in the pancreas following the administration of the contrast agent. Our subsequent studies will explore the utility in man in longitudinal studies.

Understanding the Pathogenesis of Type 1 Diabetes

Using human islets transplanted into immunodeficient mice under different glycaemic conditions, we aim to study the secretion of hormones from human islets with high resolution microscopy.

Taking GMP Grade Perivascular Mesenchymal Stromal Cells to First-in-Man Clinical Trials

Islet transplantation, where islets from donor pancreases are transplanted into the liver of patients with Type 1 diabetes, has the potential to cure Type 1 diabetes. However islets from up to 3 donor pancreases may be required for each patient because islets “engraft” or form blood vessels very poorly within the liver they are transplanted into. Working with Scottish National Blood Transfusion Service, who have manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVC) to GMP grade, we have demonstrated that when the HUCPVCs are co-transplanted with islets into diabetic mice, they promote engraftment of islets, improving blood glucose control as compared with transplantation of islets alone. This means that potentially islets from one donor pancreas may be used in the future to cure diabetes, enabling more patients to be transplanted. Our aim is to understand further how HUCPVCs improve islet engraftment and take these cells into first-in-man clinical trials.

Standardisation of preclinical PET/CT protocols across multiple research centres

This project aims to conduct a comprehensive analysis of the different factors that affect the outcome of preclinical PET/CT imaging results across multiple centres and scanners, in order to work towards standardization of small animal PET/CT imaging protocols. Standardization guidelines for preclinical PET/CT studies will help guiding the scientific community working with small animal PET/CT scanners. This is of central importance to the whole preclinical PET/CT imaging community, as the need for standardization of imaging protocols is transversal to a number of biomedical research projects.

Studying origins and heterogeneity of adipose tissue: a novel way of understanding aetiology of obesity

Despite the increased interest of preventing obesity, we know little about the origin(s) of adipose tissue. The majority of adipose tissue in our body is made up of white adipose tissue (WAT), which can be further divided into subcutaneous and visceral WAT. Our previous work, published in Nature Cell Biology, demonstrates that subcutaneous and visceral WAT differ in their developmental origins, and we identified mesothelium as one novel source of visceral adipose tissue. We are now building on this ground-breaking finding by further addressing the significance of adipose origin(s) and heterogeneity on adipose tissue development, homeostasis, and responses under diseased conditions.

The effects of endogenous and exogenous glucocorticoids on placental vascular development and hemodynamic function

Appropriate development and function of the placental vascular network is critical for maintaining fetal growth. Two questions are addressed: first, how the late gestation increase in glucocorticoids affect placental hemodynamic parameters and second, how placental hemodynamic parameters are impacted following exogenous glucocorticoid exposure, potentially resulting in abnormal fetal development.

SALTIRE 2 TRIAL

Aortic stenosis is a condition whereby one of the heart valves (aortic valve) becomes narrowed, due to calcium deposition, over time. This can lead to chest pain, heart failure and sudden death. It is the commonest valve disease requiring surgery in the developed world and as the population becomes increasingly older, it is predicted that the prevalence of aortic stenosis will double in the next 20 years. Currently the only treatment is replacement of the aortic valve. Whilst this is excellent treatment, not everyone is suitable for it. The primary objective of our study is to determine whether 2 drugs used in the treatment of osteoporosis (a condition of bone thinning) can halt/retard the progression of aortic stenosis. 

clinicaltrials.gov NCT02132026

Cardiac 23Na MRI

Absolute tissue sodium concentration is elevated in myocardial infarction and has been suggested as a biomarker for cell viability. We have developed a method to quantitatively measure cardiac sodium content in rats with good spatial resolution. This method offers a new tool for studying myocardial ion homeostasis in vivo and may be of interest for different areas of cardiovascular disease, e.g. myocardial infarction, myocardial hypertrophy, but could also be used to study other organs like kidney, liver or tumours.

Adverse cardiac remodelling under pressure overload

Myocardial fibrosis is a pathological feature contributing to the progression of a wide range of cardiovascular diseases. In this project, we validate cardiovascular magnetic resonance imaging tools to assess myocardial fibrosis in a mouse model of pressure overload.

Novel Imaging Biomarker for Detection of Regional Cardiovascular Inflammation using PET

This project aims to develop 18F-LW223, the first fluorinated radiotracer targeting the 18kDa translocator protein (TSPO) with binding to human samples independent of the rs6971 genetic polymorphism. This novel radiotracer has major potential for clinical imaging for all patients.

PET imaging biomarkers of fibrosis

This project aims to investigate the use of Positron Emission Tomography (PET) with 18F-Fluoro-Prolines for imaging and quantification of fibrosis.

Assessing the maturation, specification and function of vascular endothelial cells derived from human embryonic stem cells

We have developed a method to generate large numbers of vascular endothelial cells from human ES cells. We use this to achieve two aims: (1) to understand the molecular and cellular processes that drive endothelial maturation and specification and (2) to assess the therapeutic potential of derived cells for therapy of ischemic conditions.

Mechanisms of Pathological Adipose Remodelling

Premature diseases and deaths associated with obesity are largely accounted for not by obesity itself, but by obesity-associated conditions including type 2 diabetes, atherosclerosis, fatty liver disease, polycystic ovary syndrome, and some cancers.   Understanding adipose remodelling, and how it goes awry in “metabolic” or “insulin resistance” syndrome (IRS), is critical to tackling “obesity-related” diseases. Study of rare human disorders featuring severe abnormalities of adipose distribution and caused by a single gene defect has great value.  It can reveal hypomorphic (partial loss-of-function) mutations in genes that would be lethal if fully “knocked out” or neomorphic (“change-of-function”) mutations that perturb or change normal gene function.

Exploiting the population isolate jackpot effect

In collaboration with Prof Jim Wilson (Usher Institute) we exploit the “jack-pot effect” of human population isolates to empower genome wide association studies to identify new genes that regulate fat distribution; a major risk factor for type 2 diabetes and cardiovascular disease (CVD). We investigate the impact of the candidate genes on cellular function and whole animal physiology as part of a pre-clinical validation pipeline geared towards discovery of novel medicines for CVD.

Improving cardiometabolic health by controlling glucocorticoid delivery to adipose tissue

Glucocorticoid excess, particularly in adipose tissue, drives increased cardiovascular disease risk, including visceral obesity, hyperglycemia, dyslipidemia, and hypertension. Thus, efforts to reduce glucocorticoid action in adipose tissue as a treatment for cardiometabolic disease have both scientific and clinical merit. Our research is focused on the delivery mechanism through which glucocorticoids are ‘targeted’ to metabolic tissues, with the aims of not only advancing our understanding of glucocorticoid action in cardiometabolic disease, but identifying novel pathways to limit adverse glucocorticoid exposure.

Role of fat-associated lymphoid clusters

Some of our fat deposits, such as the omentum (the main abdominal fat) and the pericardium (around the heart) are rich in immune clusters containing IgM producing B cells important for early protection during infection. In addition, these immune clusters recruit large amounts of inflammatory cells during episodes of inflammation triggered by events such as peritonitis, pericarditis and myocardial infarction. Our lab aims to elucidate the function of these clusters and the mechanisms underlying their role in infection, inflammation and obesity.

Identifying pathways of injury and resolution in the kidney

Chronic kidney disease (CKD) is a risk factor for the development of end-stage kidney disease and cardiovascular disease. In CKD ongoing injury and attempts at self-repair occur simultaneously in the kidney, with disease progressing when the injury exceeds the ability of the kidney to repair. We are using a number of novel pre-clinical models and state-of-the-art technologies to identify pathways that may promote kidney injury or repair, so that we can develop therapies that favour regression of kidney disease.

The role of inflammation in zebrafish heart injury and repair

Embryonic and adult zebrafish are able to regenerate their hearts after injury. Using specific transgenic lines labelling immune cells and cardiomyocytes, we can use the translucent embryonic zebrafish to provide unparalleled in vivo 4D imaging of immune cell-cardiomyocyte interactions in the beating heart for up to 48 hours. Our group is characterising and manipulating these inflammatory cell events, seeking therapeutic approaches to human heart repair following injury.

The relationship between salt and glucocorticoids: implications for salt-sensitive hypertension

25-30% of people have salt-sensitive blood pressure (BP), which is an independent risk factor for cardiovascular mortality. Mechanisms underpinning salt sensitive hypertension are not fully understood. However, our recent study (Evans et al, Circulation 2016) has suggested that abnormal glucocorticoid signalling can have a major contributory role in salt sensitivity. This project will systematically analyse hypothalamic-pituitary-adrenal axis function and glucocorticoid metabolism during the adaptation to high salt diets. We will use genetic engineering approaches to understand how high salt intake increases stress hormone production and how this leads to high blood pressure.

Using Mass Spectrometry Imaging to resolve corticosteroid action in the aldosterone-sensitive distal nephron

Hypertension is highly related with cardiovascular and renal diseases. Previous blood and urine studies have shown that aldosterone and glucocorticoids are highly related with the renal regulation of blood pressure. The aim of this project is the generation of distribution maps of aldosterone and glucocorticoids on kidney tissue sections with mass spectrometry imaging that will allow us to get better understanding of the renal regulation of blood pressure in combination with the already existing data.

Adipocyte Oxygen Sensing Machinery: A regulator of metabolic disease and beyond

Obesity poses a major global healthcare challenge because it increases the risk of co-morbidities such as type 2 diabetes, fatty liver, heart disease and certain cancers. Our research focuses on mechanisms to harness adipocyte oxygen sensing to combat these obesity-related metabolic complications.

The Magnetic resonance imaging for Abdominal Aortic Aneurysms to predict Rupture or Surgery (MA3RS) study

The Magnetic resonance imaging for Abdominal Aortic Aneurysms to predict Rupture or Surgery (MA3RS) study was the culmination of 10 years’ work exploring the use of a ‘smart’ magnetic resonance contrast agent (an ultrasmall superparamagnetic particles of iron oxide (USPIO) called ferumoxytol) to identify cellular inflammation and disease activity in abdominal aortic aneurysms.

The Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial

In the SCOT-HEART trial, we demonstrated the clinical effectiveness of computed tomography coronary angiography (CTCA) in patients attending the rapid access chest pain clinic with suspected angina pectoris due to coronary heart disease. This study demonstrated that CTCA increased diagnostic certainty, changed treatments and investigations, and halved the rate of future myocardial infarction. 

Prediction of Recurrent Events with 18F-Fluoride to Identify Ruptured and High-risk Coronary Artery Plaques in Patients with Myocardial Infarction

This is a multi-centre international observational cohort study funded by the Wellcome Trust (WT103782AIA): the Prediction of Recurrent Events with 18F-Fluoride to Identify Ruptured and high-risk coronary artery plaques in patients with myocardial infarction (PRE18FFIR; NCT02278211). It is assessing whether the positron emission tomography (PET) tracer 18F-sodium fluoride is as a marker of coronary plaque vulnerability and can detect culprit and non-culprit unstable coronary plaques in patients with recent myocardial infarction.

EVOLVED TRIAL

Randomised controlled trial of early surgery in asymptomatic patients with severe aortic stenosis and objective evidence of left ventricular decompensation (myocardial fibrosis on magnetic resonance imaging) clinicaltrials.gov NCT03094143

Ion mobility Mass Spectrometry to enhance specificity of Metabolomic profiling with Mass Spectrometry Imaging

Mass Spectrometry imaging offers the chance to identify molecules in tissue sections and create regional maps of their locations. In our lab we focus on small molecular species in the metabolome, many of which are present in isomeric forms e.g. leucine and isoleucine. 

Clinical Translation: Manganese-Enhanced MRI of the Myocardium

Manganese holds great promise for cardiac MRI. As a calcium analogue, manganese-enhanced MRI provides direct imaging of viable calcium handling, with potential to define myocardial viability more accurately than with current gold-standard methods, as well as detect calcium-handling dysfunction in failing cardiomyocytes.

Reactivating ancestral heart regeneration programs in mammals

Heart failure has a poor prognosis and affects over 38 million patients worldwide. Humans have only a limited capacity to regenerate cardiomyocytes following injury. However, zebrafish possess a remarkable capacity to completely and efficiently regenerate the heart. Our goal is to identify and understand endogenous mechanisms of heart regeneration in zebrafish, and apply them to humans to promote heart regeneration following injury.

11ßHSD1 inhibition: a distinctive acute-myocardial infarction intervention for promotion of peri-infarct vascularization, reduction of infarct expansion and prevention of heart failure

There are around 915,000 survivors of myocardial infarction (MI, heart attack) currently living in the UK, many will have sustained damage to their heart that increases the likelihood of developing heart failure (HF) in the longer term. This project investigates the potential for drugs that inhibit intracellular regeneration of glucocorticoid to modify repair after heart attack by preventing infarct expansion and reducing the stimulus for the subsequent maladaptive remodeling that leads to HF.

Epigenetics regulation of endothelial cells in vascular disease

Post ischemic angiogenesis requires rapid establishment of repair machinery to enhance pro-angiogenic gene expression, as a primary requisite for vascularisation and tissue regeneration. A small number of studies have identified long non-coding RNAs (lncRNAs) that have importance for endothelial cell biology in general, but their function and consequences in angiogenesis are poorly defined. One of the major functions of lncRNAs is to regulate the target-coding gene expression by association with chromatin.

Understanding mechanisms of regeneration by resident endothelial cells in the post-ischaemic heart

The primary aim of our research is to characterise the molecular mechanisms through which resident cardiac endothelial cells contribute to vascular regeneration in the post-ischaemic heart.

Extracellular vesicle-mediated delivery of long non-coding RNA: Implications for vascular repair and regeneration

The main aim of this project is to study extracellular vesicle mediated cell-to-cell communication between human smooth muscle cells and endothelial cells, evaluate its relevance in vascular injury in an in vitro model of pulmonary arterial hypertension, and determine the significance of long non-coding RNA in this crosstalk.

5α-Reductases and risk of metabolic disease

5α-Reductases regulate metabolism of glucocorticoids and androgens. We have shown that inhibition of their activities either genetically or pharmacologically leads to increased risk of type 2 diabetes mellitus and are exploring the underlying mechanisms and degree of risk.

Brown adipose tissue as a novel therapeutic target for obesity and type 2 diabetes

Brown adipose tissue functions to increase energy expenditure to generate heat. Researchers at the University of Edinburgh are investigating how best to activate this tissue in humans as a novel therapy for obesity and type 2 diabetes.

Computational approaches to study lncRNAs in vascular biology and disease

Considering the key role of long non-coding RNAs in gene expression, we aim to identify lncRNAs showing a change in expression during vasculature development or in pathology. The lncRNA regulation and potential mechanism of action is then investigated based on genome-wide data generated by our group or publicly available.

Machine learning in myocardial infarction to improve diagnosis, risk prediction, and treatment decisions

Artificial intelligence has the potential to transform the way that we practice medicine. Our aim is to harness routine data from electronic health records, using signal processing and statistical machine learning, to develop clinical-decision support tools that will aid in the diagnosis and targeting of treatments for patients with myocardial infarction.

High-sensitivity cardiac troponin in the evaluation of suspected acute coronary syndrome

The High-STEACS research group are performing a series of stepped-wedge cluster randomised controlled trials (ClinicalTrials.gov Identifier: NCT01852123 and NCT03005158) to evaluate whether implementation of a high-sensitivity cardiac troponin I assay will reduce recurrent myocardial infarction and cardiovascular death in patients with suspected acute coronary syndrome across  tertiary and secondary care hospitals in Scotland.

High-Sensitivity Cardiac Troponin and Coronary Heart Disease

Current strategies for the assessment for coronary heart disease are imprecise with unacceptable consequences for many patients including prescription of unnecessary life-long therapies or failure to identify and treat those at greatest risk of myocardial infarction and death. Using complementary experimental, clinical and epidemiological approaches, this project is evaluating high-sensitivity cardiac troponin testing as a tool for precision medicine to improve the diagnosis, risk stratification, investigation, and treatment of patients with stable coronary heart disease.

The health effects of air pollution in Asian megacities

Globally air pollution is believed to be responsible for several million premature deaths every single year. Many megacities see the continuous exposure of many millions of people to extremely high levels of air pollution, and represent a priority for interventions to reduce pollution, exposure or the associated health effects.

The cardiovascular effects of engineered nanoparticles

There has been an exponential increase in the production and development of manufactured nanomaterials (MNMs) for wide-ranging applications. However, there is potential for MNMs to harm the cardiovascular system (as environmental nanoparticles do), yet this possibility remains largely unexplored.

The vascular effects of nanoparticles in air pollution

Air pollution is responsible for several million deaths worldwide per year, predominantly through cardiovascular mortality. The nanoparticles in traffic exhaust are especially harmful, although the biological mechanisms by which they induce detrimental cardiovascular effects remain to be fully established.

Development of an in vitro model of kidney collecting duct using mCCDcl1 cells

mCCDcl1, a mouse renal cell line, has been shown to be a good model for the study of collecting duct physiology, and cell differentiation. mCCDcl1 cells are cultured on a 3D-printed porous scaffold for the development of a 3D in vitro model of collecting duct.

A model of salt-sensitive hypertension

Too much salt in the diet can lead to an increase in morbidity, whether one is normotensive or hypertensive, but salt-sensitive hypertensives are particularly at risk. We used gene-editing technology to knockout the Hsd11b2 gene, which inactivates glucocorticoids, and have generated a model that faithfully represents the syndrome of apparent mineralocorticoid excess. 

Bioinformatics approaches to understand mechanisms of disease of cardiovascular disease

As reported by the Global Burden of Disease Study, kidney disease is one of the fastest rising causes of mortality worldwide, claiming 1.1 million lives per year. A myriad of factors can lead to kidney damage; as a vital organ filtering approximately 180 litres of blood per day, a decline in kidney function is swiftly followed by a decline in health and eventually death. The elucidation of the physiology of the kidney will enable the development of improved therapies and treatments for managing kidney diseases.

Phenotypic analysis of miRNAs to promote vessels growth

Despite the accumulating experimental evidence, the complexity of miRNA-based phenotype remains yet to be fully understood. Thus, we set to identify miRNAs that are able to regulate endothelial cell function, by performing high-throughput phenotypic screening using a whole-genome miRNA library. Furthermore, bioinformatics and network analysis demonstrated that top hit miRNAs regulate common pathways in endothelial cells, such as BMP and TGF beta signalling pathway.

The FEAT project - Female Endocrinology in Arduous Training

FEAT project logo

Women are becoming increasingly integrated into military training, and we don’t yet know how undertaking arduous roles physically affects women compared with men. We have recently identified significant health issues facing women in the military, but it isn’t known why. These issues include higher rates of physical injury (such as stress fracture) and psychological injury (such as post-traumatic stress disorder), compared with men in the military, and increased rates of referral to infertility services compared with civilian women of the same age.

Retinal optical coherence tomography (OCT): using the eye as a window on the kidney

Retinal optical coherence tomography (OCT) has transformed how we image the eye, enabling non-invasive, high-resolution, cross-sectional imaging of the retina in vivo. There is growing interest in retinal OCT as a novel method for identifying patients at increased risk of cardiovascular disease.

Glucocorticoid receptor in the early life programming of cardiac resilience

Left image: a whole mount heart from an E14.5 R26Fucci2a mouse fetus showing mCherry (red, non-proliferating) and mVenus (green, proliferating) cells. Centre image: a whole mount E10.5 mouse fetus, with blue staining indicating where glucocorticoid receptor is expressed Right image: section through the left ventricle of an adult mouse heart stained with wheat germ agglutinin (red, plasma membrane), isolectin B4 (green, vasculature) and dapi (blue, nuclei).

This research will provide important new understanding of the benefits and risks of antenatal glucocorticoid actions upon the immature heart. It will enable us to establish, in theory, areas for future refinement in therapy, for example, to avoid over treatment of babies and to limit adverse effects, whilst optimising the benefits of treatment.

VascmiR (Vascular remodelling and miRNA therapeutics)

vascmir banner

The central hypothesis of VascmiR is that microRNAs (miRs) fundamentally control pathological remodelling of the vasculature. The complexity of vascular bed heterogeneity and subsequent response to injury, the potential importance of miRNA in vascular pathology and the paucity in knowledge relating to many facets of miRNA function in the vessel wall including target pathways, mechanistic features of miRNA-mediated cell:cell communication mediated by miRNA export and uptake etc.

A classification system for zebrafish adipose tissues

Zebrafish offer a valuable model system for in vivo imaging of adipose tissue dynamics. In particular, adipose tissue can be accurately quantified in live zebrafish using fluorescent lipophilic dyes - a technique applicable to large scale chemical and genetic screens to identify modifiers of adiposity and associated disease.  Although, this methodology offers considerable promise, the comprehensive identification and classification of zebrafish ATs has not been performed.

Marie Curie IAPP Project 324325: AD-VEC

AD-VEC Logo

Adenovirus Vector Technology: Next Generation Systems for Medical Therapy (AD-VEC)

AD-VEC involves two industrial and three academic partners with the aim to identify new adenoviral vectors as vehicles in novel medical applications for cardiovascular disease and infectious disease.

This will be achieved through broad knowledge exchange between partners with complimentary and cutting edge technological and indepth skills relating to adenovirus phylogeny, biology and pathology in order to explore and exploit adenovirus existing in nature as new vectors in areas of unmet clinical need such as cardiovascular disease and infectious disease.

Does obesity lead to effects on the epigenome?

Healthy and Fatty Liver

Obesity is associated with a number of adverse effects on health including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. In this recent started programme of work we are using techniques such as DNA immunoprecipitation and ion torrent sequencing to study the role of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC) in obesity and its common sequelae.

Uncovering mechanisms for the transmission of early life programming effects across generations

Section of testis

Epidemiological studies have shown a link between exposure to an adverse environment in early life and an increased risk of cardiometabolic and neurodevelopmental disease. These ‘programmed’ effects are transmissible across generations through both male and female lines (Drake et al).

Global campaign to prevent deaths from pesticide self-poisoning

Treatment of poisoning

Acute pesticide self-poisoning hospitalizes over 2 million people every year and kills around 200,000, the vast majority in low- and middle-income countries (LMIC). Following modernization of agriculture in the 1960s during the Green Revolution, highly hazardous pesticides (HHPs) were introduced into rural households, causing an epidemic of fatal self-poisoning. Since this time, pesticide self-poisoning has killed an estimated 14 to 16 million people worldwide. Many of these deaths occur in young people, resulting in the annual loss of an estimated 10-14 million disability-adjusted life years (DALY) and immense familial and community stress.

Mass Spectrometry Imaging

MS imaging of brain

Steroid hormones circulate in blood and penetrate tissues where they have their actions. The amounts of steroids in tissue subregions can be modulated by local enzymes and transporters, making it vital to understand regional steroid amounts e.g. in inflamed sites, in tumours or in brain regions. Mass spectrometry imaging is a powerful technique used to localise molecules in tissue sections, providing molecular distribution.

Bone marrow adipose tissue: a novel regulator of cardiometabolic health?

Obesity is a major risk factor for cardiovascular disease and numerous other pathologies. Given that obesity is defined by excessive adiposity, this health burden has motivated extensive research into the formation and function of white adipose tissue (WAT; Figure 1). Such research has revealed that WAT is a key regulator of metabolic health, both as a site for energy storage and as a major endocrine organ. More recently, there has been intense interest in brown adipose tissue (BAT), which might be a new target for treating obesity and related diseases (Figure 1).

Imaging myocardial infarction

Heart images

Advanced in vivo imaging is key to cardiac phenotyping as well as for identification of myocardial injury and characterisation of structure, function and  molecular processes during remodelling of the heart in disease.

Connecting salt appetite to cardiovascular and kidney disease

kidney image

Reducing salt intake is a major health policy advocated by The World Health Organization to reduce the global burden of hypertension, Cardiovascular Disease and Chronic Kidney Disease (CKD).

The cardiovascular effects of engineered nanoparticles

There has been an exponential increase in the production of manufactured nanomaterials (MNMs) for a wide variety of applications, including engineering, electronic circuitry, food preservatives, clothes, water purification, batteries, paints, sun-creams and medical therapeutics. However, research into the potential for MNM exposure to induce toxicity is lagging behind the interest in their development.

Discovering genetic modifiers of early kidney disease

Kidney disease is a major risk factor for cardiovascular mortality. Multiple genetic and environmental factors provoke susceptibility to kidney disease. We have identified several susceptibility genes using a combination of; high-throughput transcript expression, bioinformatics and renal physiology (1). Historically we found angiotensin converting enzyme (ACE) to be a key modifier of hypertensive renal injury (2). ACE inhibitors have become frontline drugs used everyday in the clinic to tackle hypertension and kidney disease.

Steroid metabolism

The pandemic of obesity threatens to reverse the downward secular trends in cardiovascular disease because of its associations with hyperglycaemia, dyslipidaemia and hypertension (the Metabolic Syndrome). Research in Edinburgh has focused on steroid hormones as mediators of the metabolic complications of obesity and the progression to cardiovascular disease (Ann Int Med 2004, PNAS 2005).

Genetic Identification of an adipocyte-expressed anti-diabetic target in mice selected for leanness

The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains.

Vascular effects of nanoparticles in air pollution

Air pollution is responsible for several million deaths worldwide per year, predominantly through cardiovascular mortality. The nanoparticles in traffic exhaust are especially harmful, although the biological mechanisms by which they induce detrimental cardiovascular effects remain to be fully established.