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In response to the West of Scotland’s high prevalence of cardiac disease and stroke, the local biomedical community has developed a long-standing record of excellence in cardiovascular research and associated epidemiology.
The Faculty of Medicine, at the University of Glasgow, along with clinicians in local hospitals, has developed excellent basic science studying the mechanisms underlying cardiovascular disease. This is complemented by the research at the School of Pharmacy, in the University of Strathclyde, on disease models and mechanisms of action of drugs in cardiovascular disease, The Vascular Assessment Unit at Glasgow Caledonian University on the physiological and pharmacological effects of pathology and drug treatments on blood vessels, Organon Research Scotland, a drug discovery research centre based at Newhouse between Glasgow and Edinburgh with major research efforts on atherosclerosis and thrombosis and finally biotechnology companies such as Biopta Ltd, who specialise in human tissue in vitro bioassays suitable for assessment of novel cardiovascular therapies and detection of unwanted vascular side effects.
The stable and well-documented population of three million people is therefore ideal for epidemiology studies.
There are core experts researching each stage in the life of the heart as a collaborative West of Scotland exercise, with Glasgow being world leading in many of these areas.
Current studies within the Faculty of Medicine, at the University of Glasgow, along with clinicians in local hospitals, are focusing on the genetic basis of cardiovascular disease and on key areas of vascular biology.
Essential hypertension is a major risk factor for both stroke disease and ischaemic heart disease. Although 30-50% of the variation in blood pressure between individuals is attributed to genetic factors, the genes responsible are mostly unknown. Previously used strategies such as linkage analysis in families segregating for rare forms of Mendelian hypertension or exploration of several candidate genes have had a limited success. Professor Anna F Dominiczak (British Heart Foundation Chair of Cardiovascular Medicine in the Department of Medicine and Therapeutics and Headship of the Division of Laboratory Research) along with Professor John Connell (Head of the MRC Blood Pressure Group) are leading British and European studies of genetic markers (in rodent models and humans) for human essential hypertension funded by the Medical Research Council (UK-Bright Study) and the European Union (EURNETGEN). The studies are based on a genome scan strategy, which will ultimately lead to positional cloning of genes responsible for susceptibility to or severity of hypertension, left ventricular hypertrophy (precursor of Heart Disease) and sensitivity to brain ischaemia in the stroke-prone spontaneously hypertensive rat (SHRSP) with the hopeful outcome of new diagnostics and therapeutics.
For Further information see:
BHF Glasgow Cardiovascular Research Centre
A key development with an investment of £10M, this new institute will provide modern clinical and basic research facilities for the major research teams.
BHF Blood Pressure Group
MRC Blood Pressure Group
These studies are carried out in humans and in animal models, including the SHR-SP and a rabbit model of chronic heart failure. Particular focus has been placed on the regulation of the vasculature by insulin and production of key endothelial derived molecules such as nitric oxide and their involvement in Hypertension. There are major collaborative links with colleagues in the Faculty of Biomedical & Life Sciences through an MRC Co-operative Group who examine the molecular, genetic and cellular basis for cardiovascular and metabolic syndromes (Gwyn Gould, Miles Houslay, Graeme Milligan and Timothy Palmer (Division of Biochemistry and Molecular Biology), John Connell and Anna Dominiczak (Department of Medicine and Therapeutics).
The Cardiovascular Research Group, University of Strathclyde has expertise on in vivo and in vitro models of cardiovascular disease, such as ischaemic heart disease, restenosis following balloon angioplasty and pulmonary hypertension, and is interested in the modulation of receptors, ion channels, cell signalling pathways and biochemical mediators associated with these disorders. Experimental approaches include the use of isolated blood vessels and working heart preparations combined with classical electrophysiology and immunohistochemistry, and studies of platelet and white cell function. A variety of specialised techniques are employed to study isolated vascular and cardiac muscle cells.
Specialist contract research service company Biopta Ltd (a spinout of Glasgow Caledonian University), is able to provide customised solutions to tissue testing studies. Biopta specialises in human tissue in vitro bioassays suitable for pharmacological testing of most tubular tissues such as subcutaneous arteries and veins. Biopta also carries out a wide range of biochemical and cell based assays on vascular cells providing a measurement of drug sensitivity, cytotoxicity, cell activation and response to agents such as growth factors and cytokines. Biopta also offers expertise in second messenger and enzyme analysis.
Raised blood cholesterol levels are well known as a risk factor for heart disease. The basis of this has been studied for many years by a group of internationally renowned researchers led by Professors Jim Shepherd and
Chris Packard. They have explored the mechanisms of action of lipid lowering drugs and conducted large scale trials of the clinical benefit of these agents in middle aged and elderly subjects.
Current studies investigate the consequences for coronary disease of metabolic disturbances such as obesity, inflammation and lack of exercise. Other, ongoing studies are looking at the way in which fish oils influence lipid levels and coronary risk factors, and the mechanisms whereby new drugs like rosuvastatin lower dramatically the levels of atherogenic lipoproteins in the circulation.
Finally, as a follow up to the successful PROSPER multinational study new insights are being gained as to the factors that predict cognitive decline and age-related memory loss in the elderly.
Organon Research Scotland is a drug discovery research centre based at Newhouse between Glasgow and Edinburgh. It is part of NV Organon, a global Pharmaceutical Company with its headquarters in the USA. Organon is the human healthcare business unit of Akzo Nobel.
Organon has been involved in cardiovascular disorders for many years and their interest arose originally from the production of purified heparin, to prevent blood clotting. They first marketed this agent in 1948 for use in blood transfusion and the treatment of thrombosis, and for the prevention of thrombosis during certain surgical procedures. Subsequent research in the field of venous thrombosis led to the production of the antithrombotic agent Orgaran®, a heparinoid for the prophylaxis of deep venous thrombosis following surgery or ischaemic stroke, and in patients with heparin-induced thrombocytopenia. Research shows it has greater bioavailability than heparin, minimal effect on platelet function and is less likely to cause thrombocytopenia or bleeding. More recently, research has focused on atherothrombosis, the underlying cause of many peripheral, cardiac and cerebral vascular diseases. A large part of Organon's research efforts have been devoted to the production of the active chemical fragment of the anticoagulant heparin by complete chemical synthesis - a project carried out in collaboration with Sanofi-Synthelabo.
Organon was the first to model the molecular structure of antithrombin III, one in a cascade of protein molecules known to be active in the aetiology of blood clotting. Detailed structural analysis of this protein forms the basis for identifying new treatments, which prevent or treat disorders associated with blood coagulation. In collaboration with Sanofi-Synthélabo, Organon has developed a totally synthetic pentasaccharide - Arixtra® - which fits into the antithrombin III molecular shape. This has the potential to become a new therapy for the prevention and treatment of deep vein thrombosis and pulmonary embolism as well as the treatment of coronary and peripheral arterial disease. It is the first synthetic antithrombotic in clinical development and its advantages include a reduced potential for causing haemorrhagic complications. Their current research builds on the experience gained from their anti-thrombotic expertise. Novel mechanisms which interfere with the clotting process are in the early phase of development and they have identified molecules for clinical development which have demonstrated efficacy in their models and which exceed the performance of novel entities either in the clinic or in development elsewhere.
In addition to research efforts in thrombosis, Organon’s primary interest is now in atherosclerosis. The prevention of clinical syndromes such as angina, myocardial infarction and stroke become increasingly prevalent in the early 40s in men, and after the menopause in women. They have focused on processes and mechanisms, which affect the rupture of atherosclerotic plaques and on the exposure of the thrombotic core to blood. Organon’s understanding of atherosclerosis biology is progressing rapidly and it is clear that mechanisms, which modulate the substantial inflammatory component to the disease, afford considerable potential for intervention. This understanding has identified several strategies that have led to Organon's focus on mechanisms, which they believe will make a substantive difference to the progression of the disease, and specifically target the root cause of clinical events.
For further information contact Dr Heather McKinnon, Team Leader Atherosclerosis or visit the Organon UK website
The West of Scotland has been the focus of several large cardiovascular investigations into primary coronary prevention. The West of Scotland Coronary Prevention Study (WOSCOPS) led by Professors James Shepherd (Director) and Stuart Cobbe (Co-Principal Investigator), was a landmark primary prevention trial of the drug Pravastatin in 6,000 middle-aged men. The study showed, for the first time, the benefits of a lipid-lowering drug in reducing the risk of heart attack in established and non-established cases of heart disease, coronary mortality and deaths from any cause. This research has been extended in the PROSPER Study, focusing on reducing the incidence of coronary episodes with pravastatin in the elderly population. In addition, 2 major epidemiological projects, ‘The Living Heart Study’ (funded by the BHF) and the Beacon Study (funded by the Scottish Office), are examining left ventricular function and the cost-effective use of natriuretic peptide hormones as detectors of left ventricular dysfunction (a precursor of heart failure) in the North Glasgow Community respectively (Prof Henry Dargie, Dr McDonagh, Dr Robb, Department of Cardiology and Exercise Medicine, Glasgow Royal Infirmary).
For further information see West of Scotland Coronary Prevention Study (WOSCOPS)
There are therefore benefits in identifying at-risk patients as early as possible. Professor Henry Dargie has been leading an appeal to raise over £2M for a magnetic resonance imaging heart scanner, which would be the first in Scotland. It works by taking very accurate images of the heart and coronary arteries and would provide safe, non-invasive, reliable and early detection of heart disease to hopefully avoid the need for bypass surgery.
For further information see Development news: Bypassing the Bypass
Instrumental to the WOSCOP’s, PROSPER and the British Regional Heart Study have been the development of computer software for long-distance analysis of electrocardiograms (ECG’s) by Professor Peter Mcfarlane (Professor of Electrocardiology, Department of Cardiology and Exercise Medicine, Glasgow Royal Infirmary) which provided interesting electrocardiographic observations in relation to risk factors for ischaemic heart disease. Professor McFarlane currently directs an ECG Core laboratory based at the Glasgow Royal Infirmary, which handles ECGs recorded in national and international clinical trials and epidemiological studies. The Group has extensive commercial collaboration with what is now Spacelabs Burdick and Siemens both of whom market the Glasgow ECG analysis program worldwide.
For further information see ECG Core Laboratory
Chronic heart failure (CHF) is associated with a high mortality. Death is caused either by progressive pump failure or by abnormal heart rhythms resulting in sudden cardiac death. In the myocardium, research programmes funded by the British Heart Foundation and led by Professor Stuart Cobbe of the Department of Medical Cardiology at the Royal Infirmary and Professor Godfrey Smith, aim to define the mechanisms responsible, including the electrical properties of cells in the heart muscle and the origins of irregular heart rhythms. In particular, they have developed novel techniques for imaging calcium dynamics in myocytes from the failing heart to identify the relationship to changes in contractile function.
For further information see Cardiology and Exercise Medicine Research activities
Other research in this area includes a collaborative patch clamp study in human atrial cells by Professor Kathleen Kane (Cardiovascular Research Group, University of Strathclyde) and Dr Andrew Rankin’s group at the Glasgow Royal Infirmary, to identify the changes in ion channels that occur as a consequence of a common arrhythmia, atrial fibrillation. Additional work has been carried out on the functional and ionic properties of cells isolated from the atrio-ventricular node which play a key role in transmission of responses from the atria to the ventricles, being one of only a few groups in the world who can do work in this cell type. One of the clinically used drugs they have investigated is adenosine, which appears to have different effects on atrial and AV nodal cells. Such abnormal heart rhythms are of great interest as they can be caused or exaberated by Myocardial Ischaemia (heart attacks) and hypertrophy (enlargement of the heart).
For further information see Cardiovascular Research Group, University of Strathclyde
If the human heart valve fails, it can be replaced with a biological valve, usually incorporating tissue from pigs, or a mechanical valve. But mechanical valves need lifelong anticoagulation; biological valves do not last in children and even in adults, most fail within 10-15 years and typically last only 15-20 years. Glasgow University’s Department of Cardiac Surgery in partnership with AorTech Europe Ltd and Liverpool and Leeds Universities have done extensive laboratory tests to evaluate valves made of synthetic material. The life-giving and cost-saving potential of these artificial valves is enormous in the treatment of valvular heart disease. The research programme was supported by a MedLINK research grant and led by Professor David J Wheatley (British Heart Foundation Professor of Cardiac Surgery, University of Glasgow, Honorary Consultant Cardiothoracic Surgeon, Glasgow Royal Infirmary) and has resulted in the development of a new tri-leaflet valve, made entirely from polyurethane which aims to replicate the natural functioning of a living heart valve (aortic valve). It is now in the process of commercial exploitation with the hope of targeting the worldwide market in both biological and mechanical heart valves. A clinical study investigating coagulation activation markers and risk of cardiovascular events in patients with prosthetic heart valves is underway, in collaboration with colleagues in the Thrombosis and Haemostasis Research Group.
Led by Prof. John J.V. McMurray (Professor of Medical Cardiology and Honorary Consultant Cardiologist, Western infirmary), this group's focuses on the epidemiology, vascular pathophysiology, clinical pharmacology, clinical trials and multidisciplinary management of chronic heart failure (CHF). Interest has been placed on reducing morbidity and mortality by attenuating vasoconstrictor pathways (e.g. the renin-angiotensin system and the sympathetic nervous system) and vasodilator pathways. In addition John Mcmurray is co-chair of the VALIANT (the VALsartan In Acute myocardial iNfarction Trial), a long-term trial conducted on survivors of heart attacks with a new type of high blood pressure medication called valsartan. Notably valsartan has been shown to reduce death and prevent recurrent heart attacks in patients as well as standard Ace inhibitor treatment, hopefully giving physicians an alternative choice of therapy for their patients.
For further information see Heart Failure Research Group
The Vascular Assessment Unit (VAU) is a major contributor to cardiovascular research in Scotland. Founded in 1996, the VAU has consistently focused its research on understanding the physiological and pharmacological effects of pathology and drug treatments on blood vessels. With internationally acknowledged expertise in functional assessment using in vitro technologies the VAU has core interests in three clinical areas. These are cardiology, women's health, and peripheral vascular disease as well as a number of long-standing projects investigating basic mechanisms of vascular biology. Currently, the VAU has a number of external research collaborations including projects in the US, Europe and Asia.
In collaboration with Professor John McMurray, (Dept of Medicine and Therapeutics, University of Glasgow) and an excellent support team at the Western Infirmary in Glasgow, the VAU has maintained a biopsy programme for over five years allowing powerful blinded studies of the vascular effects of chronic heart failure (CHF). In particular, the complex role of different neurohumoral factors in the pathophysiology of CHF has been investigated and the VAU has published extensively on the mechanisms underlying the vasoactivity of a number of circulating hormones in human tissues. These have included endothelin, angiotensin II, adrenomedullin, and relaxin. In 2002, The VAU was one of the first groups to characterize the function of the novel peptide urotensin II in human blood vessels.
Similarly, collaborations with the Department of Surgery at Stirling Royal Infirmary, Department of Optical Engineering in the University of Loughborough, and Professor JC McGrath's Autonomic Unit (University of Glasgow) combine to allow the determination of vascular changes that occur as a consequence of peripheral vascular disease.
Adaptive changes during obstetric events and those relating to gynaecological pathologies are studied in collaboration with research teams in Glasgow (Dr Mary Ann Lumsden and Professor Ian Greer), Manchester (Professor Phil Baker, University of Manchester), Oxford (Dr Leonid Nikitenko, University of Oxford), and Romania (Professor Maya Simonescu, University of Bucharest, Romania).
For further information contact Dr Chris Hillier
In parallel to vascular studies on the implications of nitric oxide in hypertension and cardiovascular disease conducted by the BHF Blood Pressure Group, several laboratories have been developing gene transfer/therapy strategies in rodent models such as the stroke-prone spontaneously hypertensive rat (SHRSP) with adenoviral or adeno-associated viral vectors used, for example, to over express protective vascular genes such as vascular endothelial growth factor or endothelial nitric oxide synthase as a means of improving the function of diseased vessels. Longer-term vectors (>3 months) are being developed and genetic retargeting strategies employed to examine local and systemic effects of these genes on blood pressure regulation and vessel integrity. They hope to directly transfer these discoveries to essential hypertension in humans (Dr J Brosnan, Professor Anna F Dominiczak).
For further information see BHF Research Interests
At the same time as scientists have been discovering more about heart disease and its treatment, others have been active in promoting prevention.
Through the University of Glasgow’s Centre for Exercise Science and Medicine (CESAME), a joint venture linking the Institute of Biomedical & Life Sciences (IBLS) and the Faculty of Medicine and chaired by Professor Ian McGrath, research programmes are underway with Professor Stewart Hillis, Dr Jason Gill and others investigating the role of exercise as a means of rehabilitation in cases of cardiac disease as well as the development of preventative models for the promotion of physical activity. Some of their recommendations have being implemented across the University community through such projects as the 'active commuting' programme involving staff from across the campus.
For further information see CESAME
Cardiovascular research interests of Dr Chris Hillier and Dr David Bunton within the Department of Biological and Biomedical Sciences at Glasgow Caledonian University, resulted in the formation of a spinout company, Biopta Ltd, that provides specialist contract research services and develops novel instrumentation for the pharmaceutical and biotechnology industry such as 'Perf-Exion'; a tissue analysis instrument which will greatly accelerate the assessment of drug-tissue interactions.
Biopta carries out experiments on living tissue that have a number of applications, for example, they allow assessment of novel therapies, detection of unwanted side effects and they allow comparisons to be made between different formulations, delivery methods or different patient groups.
Biopta is able to provide customised solutions to tissue testing studies. The company specialises in human tissue in vitro bioassays suitable for pharmacological testing. Biopta also carries out a wide range of biochemical and cell based assays on cells providing a measurement of drug sensitivity, cytotoxicity, cell activation and response to agents such as growth factors and cytokines. In addition they offer expertise in second messenger and enzyme analysis.
For further information contact Nicola Barnstaple, Business Development Manager:
Or visit Biopta Ltd Website
Glasgow School of cardiovascular studies
PharmaLinks
BHF Blood Pressure Group
MRC Blood Pressure Group
MRC Co-operative Group
Cardiovascular Research Group, University of Strathclyde
Thrombosis and Haemostasis Research Group
Heart Failure Research Group
Autonomic Unit, University of Glasgow
ECG Core Laboratory
CESAME
AorTech Europe Ltd
Biopta Ltd
Organon UK website
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