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About Cardiovascular Medicine, MSc - at University of Sheffield

Lead academic: Dr Victoria Ridger

The discovery of effective and novel treatments for heart disease starts with understanding the molecular and cellular processes involved. These approaches, along with disease processes in model systems, are well established in our department, with some of the world's foremost research in these areas being conducted in Sheffield.

The course is delivered by experts within the cardiovascular field. It provides a unique research environment within which you can learn valuable transferable skills encompassing the full range of activities from discovery science at the laboratory bench to the hospital clinic or bedside. A research project forms the major part of your studies, during which time you will be integrated into the department as a member of an established research team.

Projects

The research project forms a major part of your studies. Many of our students have successfully published findings from their research projects. Here are some examples of the types of projects that may be available (the projects listed may differ from the projects available):

Modelling blood flow to improve the management of coronary artery disease.

Supervisor:Professor Julian Gunn

In order to develop an accurate model of blood flow in patients with coronary artery disease (CAD), you will

• learn about decision-making in the management of CAD
• learn about the physiology of coronary blood flow in health and disease, including fractional flow reserve (FFR)
• familiarise yourself with our VIRTUheart model of virtual (computed) FFR
• work on improving the accuracy of the model

We have a wealth of clinical data (angiograms and measured FFRs) in our research archive (ArQ). You will have full access to these data and will be able to process the angiograms in the VIRTUheart software and produce your own measures of virtual FFR for your individual project. This will include aspects such as investigating the effect of branched vessels, diffuse disease, chronic occlusions, grafts, vascular distensibility, myocardial ischaemic burden, acute coronary syndromes and 'virtual' stunting.

You will be taught about coronary anatomy, angiography, angioplasty, bypass surgery, image processing, using software tools, data analysis and report writing.

Investigating a novel anti-inflammatory role for statins through modulation of neutrophil microvesicle production

Supervisor:Dr Victoria Ridger

Cardiovascular diseases (CVD) account for 31% of all global deaths. Atherosclerosis, an accumulation of fibro-fatty plaques in the vessel wall, is a major underlying cause of CVD. High cholesterol levels are a risk factor for developing atherosclerosis and lipid-lowering statins decrease plaque progression. However, statins also have effects beyond cholesterol lowering, including modulation of microvesicle production. Microvesicles are membrane-derived sacs released from cells, which contain cellular material and express molecules derived from the parent cell. Neutrophil microvesicles exacerbate vascular inflammation in atherosclerosis by activating endothelial cells through delivery of their cargo, including microRNA.

This project will investigate whether statins can modulate neutrophil microvesicle function by inhibiting their release or altering their content. The project will involve cell isolation techniques, tissue culture, flow cytometry, qPCR, ELISA, immunoblotting and immunocytochemistry.

Serological and imaging biomarkers in the assessment of right ventricular failure in pulmonary arterial hypertension.

Supervisor:Dr Andy Swift

Pulmonary arterial hypertension is a severe disease associated with poor outcomes due to failure of the right ventricle. Reliable monitoring of the right ventricle and identification of right ventricular failure is crucial to delivering the optimal therapeutic approach.

Specific serological biomarkers have been identified as useful prognostic markers particularly at follow-up, strongly predicting all-cause mortality. In addition, several novel serological biomarkers are emerging with great potential for both diagnosis and prognosis in PAH. Magnetic resonance imaging is considered the gold standard test for the evaluation of the right ventricle.

The ambition of this research is to determine the clinical value of serological biomarkers and compare them with MRI in patients with PAH. This study will include exposure to lab-based and clinically applied research; the student will be required to develop core lab skills coupled with competency in cardiopulmonary MRI analysis.

The role of a novel inflammatory macrophage marker in human immunity responses.

Supervisor:Dr Heather Wilson

In the artery wall, macrophages play an important role in driving atherosclerosis, by taking up lipids and forming the necrotic lipid core that builds plaque deposition. Macrophages show plasticity between different states or phenotypes, according to their functions in the inflammatory response to infection; clearing pathogens, and in the resolution and repair response following injury or infection.

In order to analyse how macrophages change within diseased arteries, we discovered a novel membrane protein marker for the inflammatory phenotype.

This project will build our understanding of the function of this novel membrane protein. We hypothesise that this protein is involved in the inflammatory macrophage response to lipid uptake, phagocytosis and pathogen sensing. You will perform siRNA knockdown of this protein in human monocyte-derived macrophages, to assess its role in phagocytosis, pathogen clearance and lipid loading.

Investigating the role of filamin A in pulmonary arterial hypertension

Supervisor:Dr Allan Lawrie

Cytoskeletal proteins that bind to actin to cross-link actin filaments, and can also act as a protein scaffold for numerous protein partners. Mutations in specific cytoskeletal proteins are associated with severe arterial abnormalities, and through whole genome sequencing, we have recently identified causal mutations in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH). How these mutations link to the molecular and cellular pathogenesis of IPAH is unknown.

You will investigate the expression and function of these genes in pulmonary artery smooth muscle cells and endothelial cells from patients with IPAH and controls as well as lung tissue from rodent models and post-transplant heart and lungs.

Investigation into the effects of ticagrelor on plasma adenosine levels

Supervisor:Professor Rob Storey

The PLATO study demonstrated that ticagrelor, a platelet P2Y12 receptor antagonist, reduced mortality in patients with acute coronary syndromes (ACS) compared to standard therapy with clopidogrel.

While it is well established that ticagrelor results in higher and less variable platelet P2Y12 inhibition than clopidogrel, it is hypothesised that the observed effect on mortality rates may relate to additional effects of ticagrelor. These off-target effects of ticagrelor may be attributable to its ability to selectively inhibit adenosine uptake by erythrocytes via equilibrative nucleosidase transporter 1 (ENT1) and inhibit platelet-expressed ENT1. Inhibition of ENT1 may result in increased plasma adenosine levels.

Studies looking at plasma adenosine levels following ticagrelor therapy have shown conflicting results; an increase in plasma adenosine has been observed in patients with ACS and peripheral vascular disease but a study in healthy volunteers and a study carried out in Sheffield in patients undergoing elective coronary artery stenting have shown no effect.

This research project will obtain additional information on the effect of ticagrelor on plasma adenosine levels and identify potential explanations for the discrepancies observed between clinical studies.

Hemodynamics of stents and effects on vascular healing

Supervisor:Professor Paul Evans

Stents alter local flow patterns which have major effects on inflammation, vascular dysfunction and restenosis.

To understand the molecular mechanisms linking flow to vascular function, you will use state-of-the-art cell culture and molecular biology techniques to elucidate the effects of flow on coronary artery endothelial function. This will include the use of unbiased microarray/RNAseq omics approaches coupled with gene silencing technology to assess the function of flow-sensitive genes.

The project will equip you with modern molecular techniques that are required for postgraduate molecular medicine research at the PhD level.

Computer modelling in treatment management of patients with aortic valve stenosis

Supervisor:Norman Briffa

Aortic valve stenosis is the most common valvular disease in the UK and its prevalence is rising with an ageing population. Symptomatic patients have a poor prognosis and the only effective treatment is aortic valve replacement (AVR). This can be performed during open heart surgery or in certain cases using transcatheter techniques.

Symptomatic and haemodynamic improvement (decrease in gradient and myocardial work) after AVR is dependent on several factors including the size and type of the implanted prosthesis and function of the left ventricle. Computer modelling and artificial intelligence (AI) are increasingly being used in medicine to help physicians make diagnoses and/or choose appropriate treatments.

Using a computer model that was developed by the Eurvalve project, we hope to predict the degree of change in haemodynamics, cardiac work and symptoms that will occur after AVR. Validation will take place using data from patients who already have received their treatment and the model will be used prospectively in 20 patients with aortic stenosis undergoing treatment.

The role of RNA editing in the pathogenesis of pulmonary arterial hypertensionitle

Supervisor: Dr Roger Thompson

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by vascular remodelling that leads to increased resistance in the pulmonary circulation, right heart failure and premature death.

The bone morphogenetic protein (BMP) signalling pathway is strongly implicated in disease susceptibility, with mutations in the BMPR2 gene found in approximately 15% of patients with the idiopathic disease and over 70% of patients with the heritable form of the disease. Reduced BMPR2 signalling in the absence of mutations has been widely reported in patient cells and tissue and in animal models of pulmonary hypertension, but how signalling is suppressed in this context remains unclear.

RNA editing is a post-transcriptional modification that promotes transcriptional diversity across tissues and can alter protein translation, stability, structure or function. Compelling evidence has emerged to implicate adenosine-to-inosine (A-to-I) RNA editing in vascular biology by ADAR1, the master regulator of A-to-I editing in vascular cells; however, the roles of these pathways have not been examined in PAH. The goal of this project is to determine whether ADAR1 regulates pulmonary vascular remodelling.

Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) for precision medicine

Supervisor: Dr Pankaj Garg

We have several themed projects which involve cutting-edge 4D flow technology to improve diagnosis and guide therapy in cardiac disease. The projects involve enhanced evaluation of valvular heart disease, heart failure and pulmonary hypertension using 4D flow CMR. Sheffield is uniquely positioned to offer these opportunities as we have a high computational lab at the Imaging Sciences lab located in POLARIS.

This project will equip the students with the following skills:

• Advanced critical insight into cardiovascular physiology using imaging-based methods.
• Segmentation of heart MRI for deriving physiologically relevant functional and tissue characterisation parameters.
• Understanding of software solutions for heart MRI analysis.
• IT skills including collaborative writing, handling referencing software, visualisation and curation of large datasets.

The student will be expected to publish at least two papers from this project under the supervision of Dr P Garg and Dr A Swift. They will be encouraged to present their findings at national/international conferences.

This course will

• provide you with a good understanding of basic science as well as some clinical insight into pathological conditions
• give you insight into cutting-edge research, both in the lab and in the clinic
• provide you with experience of a hypothesis-driven laboratory research project alongside experts in the field

All of the above will increase your employability in both industry and academia, as well as being an excellent route to a PhD. It will also provide valuable transferable skills that you can use in whatever career path you choose.

Intercalation

We accept medical students who wish to intercalate their studies. Find out more on the School of Medicine and Population Health website.

Do you have a question? Talk to us

Book a 15-minute online meeting with our course tutor to find out more information and ask further questions.

Book an appointment with Dr Victoria Ridger

Notes about fees for this course

The fee listed is for the advertised mode of study. If you're studying for an alternative qualification or via a different mode of study (eg full-time, part-time) then the fee could be different. Due to inflation, the fee for Home students could also increase after your first year of study. Use Sheffield's fee calculator or contact the Student Fees team to check.

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