Cardiac & Vascular diseases

Medical Research Scotland is one of the largest and most comprehensive independent research charities in Scotland. Unlike most medical research charities, our funding isn't restricted to any one disease or condition, we support high-quality research that aims to improve the understanding, diagnosis, treatment and prevention of all diseases and disease mechanisms.

Awards in the past 20 years

The following are some of the awards we made for research into cardiovascular disease.

logo Dr William Dempster (Mechanical & Aerospace Engineering, Strathclyde University) to supervise Faidon Kyriakou during his PhD Studentship, "Development of analysis methods for patient specific aneurysm repair devices". This research will involve close working with Vascutek Ltd.
The occurrence and rupture of an aneurysm in the lower abdominal artery is the tenth most likely source of death in men over the age of 55. If the existence of an aneurysm is identified then stent-like technologies have been developed over the past 10 years to allow for deployment, structural support and to provide adequate blood flow to mitigate against aneurysm wall rupture. While devices are in clinical use it has been established that most patients have a unique artery topography that require tailored solutions. The design of such devices is in its infancy and the inability to measure the failure stress state of a device when deployed in a human artery necessitates the use of computational modelling tools. The overall aim is to develop simulation tools to allow medical device manufacturers to minimise mechanical failure and to enhance the overall performance of devices that are specially tailored for patient's anatomy. The project significantly builds on engineering simulation methods (previously developed by Dempster & Nash). To date, this has primarily focussed on deformation issues of the key structural elements of the devices. The proposed research will require novel simulations to address a number of new issues for "tailored" devices, including full device modelling, the inclusion of fluid-structure interactions and the need to address uncertainty issues in device design and deployment. This will allow the simulation techniques to be applied with real confidence in a design context. In this study the analysis techniques will be applied to device designs of Vascutek Ltd. These consist of tubular fabric constructions supported by a series of wire bundles wound from strands of super-elastic material Nitinol. The functionality and long-term mechanical life of the device depends on understanding of the device - artery interactions which the simulation techniques will deliver.

Professor Emanuele Trucco (School of Computing, Dundee University) to supervise Andrew McNeil during his PhD Studentship, "Whole body MRI clinical atheroma analysis". This research will also involve close working with Toshiba Medical Visualisation Systems
Cardiovascular disease (CVD) is the leading cause of mortality in the UK and was responsible for over 50,000 premature deaths in 2008. The economic burden of CVD continues to rise, the overall annual cost in the UK is £30bn. The burden of cardiovascular disease is predicted to increase due increased obesity, high blood pressure, type 2 diabetes and old age. While about half (48%) of deaths are from coronary disease (CHD) and a quarter (28%) from stroke, the burden of CVD is spread across the different vascular territories within an individual. For instance, 40% of patients with leg arterial disease (PAD) have neck arterial disease with a risk of stroke, or kidney arterial disease, with a risk of high blood pressure and kidney failure, while the majority die of undetected CHD. Identification of the severity and distribution of the burden of CVD in different vascular territories in an individual presenting with cardiovascular symptoms, e.g. leg, at an early stage would be expected to alter patient management and lead to improved patient outcomes. This staging of cardiovascular disease is analogous to the disease staging undertaken in cancer. Whole body cardiovascular MRI (WBCVMR) offers a new, non-invasive, single point, comprehensive cardiovascular disease imaging assessment which, when combined with a new quantitative analysis technique, could provide the necessary assessment of CVD distribution, severity and risk of early mortality. The key research challenge is to develop a robust image processing analytical tool that can quantify disease from the MBCVMR examination.

Professor Colin Campbell (School of Chemistry, Edinburgh University) to supervise Miss Hannah Johnston during her PhD Studentship, "Systems redox biology analysis of a novel family of naturally-derived anti-oxidants/anti-inflammatories". This research will also involve close working with Aquapharm BioDiscovery Ltd.
The regulation of cellular redox potential is important in controlling the behaviour of healthy cells and its dysregulation is implicated in the initiation and proliferation of several disease states. Redox potential is a measure of the driving force for oxidation and oxidative changes are known to be important in the initiation or proliferation of a variety of diseases including arthritis, chronic obstructive pulmonary disease (COPD), Alzheimer's disease, age-related macular degeneration and multiple sclerosis. Aquapharm Biodiscovery Ltd. has recently discovered a new family of molecules which have therapeutic potential as anti-oxidants or anti-inflammatory drugs in diseases such as those listed above. It is thought that this family of molecules works by interacting with pathways involved in cellular redox regulation. Our aim in this project is to use a combination of cutting-edge biophysical techniques, established molecular biology assays and a new approach to visualisation and interpretation of this data to understand the mode of action of Aquapharm's therapeutic molecules with a view to optimising their effect. Through combining quantitative measurements with a systems biology approach we will produce a quantitative map of redox potential distribution in the cell that offers a completely new way to analyse the effects of molecules which alter redox-regulation.

Dr David Meek (Medical Research Institute, Dundee University) to supervise Mr Sumanth Iyer during his PhD Studentship, "Improving the sensitivity of a novel PIM kinase-targeted therapeutic agent, CXR1002, through identification and modulation of cross-talking pathways". This research will also involve close working with CXR Biosciences
PIM protein kinases are a group of highly related signalling molecules that normally regulate the growth and survival of cells. Failure of cells to regulate these molecules occurs in a range of diseases including cancer. The development of drugs that inhibit these molecules offers the potential to block the contribution PIM kinases make to the development of disease. Defining pathways that interact or cooperate with PIM will improve understanding of basic disease processes. Defining approaches to improve sensitivity to the recently-developed PIM inhibitor (CXR1002) should benefit continued clinical trials and, ultimately, effective patient treatment.

Dr Heather Wilson* (Institute of Medical Sciences, Aberdeen University) to supervise Miss Miriam Obliers during her PhD Studentship, "Novel small molecule modulators of the antioxidant response pathway: potential for therapy in cancer/inflammatory disease". This research will also involve close working with Aquapharm BioDiscovery Ltd.
This project aims to develop a tiered screening strategy to detect the activity of novel secondary metabolites from purified extracts of marine organisms which show promise for the potential future development of new anti-cancer and/or anti-inflammatory drugs. The work will first try to identify which purified compounds show strong functional activity, but with minimum cell toxicity or induction of apoptosis, then the specific mechanisms and cell signalling pathways involved which allow these compounds to exert their functional ability. Thereafter, their pharmacological effects, in both in vitro model tumour cell systems and established inflammatory cell systems. Understanding the mechanisms of action and likely clinical effectiveness of potent, non-toxic and non-electrophilic compounds derived from natural marine-based secondary metabolites will be of huge benefit in developing lead compounds with minimum 'off target' effects for these two important therapeutic areas.
[*Dr Wilson took over this award, following the death of Professor Hawksworth, to whom it was made originally.]

£148,872 over 36 months to Dr Richard Mort & Professor Iain Jackson (Medical & Developmental Genetics, MRC Human Genetics Unit, Edinburgh) & Dr Kevin Painter (Mathematics, Heriot-Watt University), to take an integrated multidisciplinary approach to modelling normal neural crest cell development and the abnormalities that contribute to human birth defects.
1 in 3,000 babies born in the UK are diagnosed with neurofibromatosis type 1 (Nf1). As well as having an increased risk of developing cancers of the nervous system, >95% of children diagnosed with Nf1 also have variable amounts of skin and hair hyper- or hypopigmentation. Pigment cells are a subtype of neural crest stem cells (NCSCs), the migration of which is a fundamental antenatal development process. Using a unique integration of live imaging and mathematical modelling, this project aims to explain neural crest cell behaviour in these and related disorders.

The first Support Fellowship of £150,000 was awarded to Dr Colin Berry, Scottish Senior Clinical Research Fellow (BHF Glasgow Cardiovascular Research Centre, Glasgow University), for his work on combining computer modelling and MRI to improve heart attack treatment
Heart attack is the leading cause of premature ill health and death in Scotland and worldwide. It is a particular problem because not only is it difficult to predict, but the nature and severity of damage to the heart is difficult to detect. Echocardiography is often carried out immediately after a heart attack, to give doctors an indication of the functionality of the heart. But it cannot tell if there is any swelling or bleeding, so the true extent of the heart damage is not known. Magnetic Resonance Imaging (MRI), is the gold standard way to measure heart function. It provides images of the beating heart, is non-invasive and, unlike a CT scan, does not involve harmful X-rays, so is safe to use and repeat  - even in heart-attack patients. This project is developing new computer models of heart attack and combining them with the power of MRI scans, aiming to find better ways to prevent or treat heart attack in the future.

£139,339 over two years to Dr Pasquale Maffia & Dr James Brewer (Strathclyde Institute of Pharmacy & Biomedical Sciences, Strathclyde University), for the visualisation of antigen presentation in models of atherosclerosis.
Cardiovascular diseases are the most common causes of death in Scotland and are expected to be the main cause of death globally within the next 15 years. New strategies for prediction, prevention, and treatment are needed. Immune responses are known to be important in atherosclerosis ('hardening' of the blood vessels), but the detailed mechanisms remain unknown. Using state-of-the-art technology (multiphoton microscopy) in animal models, this project will, in real time, investigate the detail of all the components of the immune response. The aim is to provide the detail needed to improve current therapeutic approaches and reduce cardiovascular morbidity and mortality.

£80,000 to Dr Christopher Michael Loughrey (Cell Sciences, Veterinary Medicine, University of Glasgow) & Professor Godfrey Smith (Biomedical & Life Sciences, University of Glasgow) for a two-year investigation of the role of intracellular calcium in left ventricular diastolic dysfunction.
The heart's ability to pump blood through the body and then refill again is partly dependent on the action of calcium stored in the heart muscles. In 'heart failure' the heart cannot relax sufficiently for filling. This project will investigate whether the cause is a change in how the calcium works.

£69,347 over two years to Drs Roger W. Brown & Stewart Fleming (Molecular Medicine Centre, Edinburgh University) for a study involving the identification of novel corticosteroid regulated genes and molecular pathways contolling renal sodium balance and blood pressure.

£19,400 to Professor Jill F. Belch (Vascular Medicine & Biology) Mrs Rosemary Levison (Vascular Laboratory) Profesosr Annie Anderson (Centre for Applied Nutrition Research), Dr J. Stewart Forsyth (Child Health) and Dr Faisel Khan (Vascular Medicine & Biology, Dundee University and Ninewells Hospital & Medical School) for the purchase of equipment for research into aortic compliance, measured by ultrasound echo tracking, as an early marker for vascular disease.

£42,647 over two years to Dr Paul Neary (Medical Cardiology) & Professor Godfrey Smith (Biological & Life Sciences, Glasgow Unviersity) to investigate the characteristics of spontaneous SR Ca2+ release in failing human myocardium.

£61,405 over 18 months to Dr Rona L. Carmichael, Proessor Nigel R. Webwter & Dr Helen F. Galley (Anaesthetics & Intensive Care, Aberdeen University) for a study of the interleukin-8 gene and abnormalities of gas exchange following cardiopulmonary bypass.

£61,457 to Drs Robin P. Alston, Michael Souter and Sheena Miller (Anaesthetics, Edinburgh Royal Infirmaty) and Dr Peter J.D. Andrews (Anaesthetics Western General Hospital, Edinburgh) for a one-year investigation into whether postoperative cerebral hypoperfusion only occurs following heart surgery.

Mrs Jean V. Baxter Medical Research Fellowship 1995-97 was awarded to Dr Martin McIntyre (Medicine & Therapeutics, Western Infirmary Glasgow) for a study of endothelial nitric oxide deficiency in cardiovascular disease and its consideration as a target for genetic manipulation.

£100,000 as a capital grant to Professors Henry Dargie (Medicine & Therapeutics), Ian McGrath (Physiology) and Stuart Cobbe (Medical Cardiology, Glasgow Royal Infirmary) all of Glasgow University, to fund the provision of a suite of five research laboratories as part of the University's Clinical Research Initiative into cardiovascular disease.

The Cruden Medical Research Scholarship 1993-94 was awarded to Dr Robert I. Cargill (Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee) to study the effects of vasoactive peptides on the pulmonary vascular bed.

£105,793 over three years to Dr Anna F. Dominiczak & Professor John L. Reid (Medicine & Therapeutics, Glasgow University), Dr Marek H. Dominiczak (Biochemistry, Western Infirmary Glasgow) & Dr Christopher J.K. Packard, Professor James Shepherd & Dr Dairena Gaffney (Biochemistry, Royal Infirmary Glasgow) to investigate the biochemical, cellular and genetic characteristics of familial hypercholesterolaemia in the west of Scotland.