In May 2007, £423,208 was awarded to the following projects in the Basic Science grant category.
Leeds Institute of Molecular Medicine | £6,000
9 month project
Abdominal Aortic Aneurysm (AAA) is a common condition that affects men over the age of 65. The aorta, the main artery leading from the heart, expands below the level of the kidney arteries and with time there is a significant risk of rupture and death. The cause of this expansion is not known and hence prevention or early interventions are not possible.
This current project will be a continuation of previously funded work and is aimed at better understanding the molecular events that lead to AAA in order to devise better strategies for treatment and even prevention.
University of Bristol | £56,100
36 month project
In some pathological conditions the fluid that surrounds the heart cells becomes acidic. This can occur as a result of metabolic changes in the body and also- importantly- when the blood supply to heart tissue becomes compromised, as occurs during a heart attack. Acidosis decreases contraction of the heart and increases the risk of dangerous arrhythmias occurring. It is thought that this increased risk of arrhythmia results from changes in the function of ion channels in the heart, but the effects of acidosis on some types of ion channels involved in the electrical activity of the heart are incompletely understood.
The results of this project will provide valuable insights into how the function of an important cardiac ion channel is altered when heart tissue is exposed to acidosis. The resulting information will lead to an increased understanding of how the normal electrical activity of the heart is adversely affected by acidosis and becomes increasingly liable to generate arrhythmias.
Kings College London | £84,976
Evidence suggests that diets containing natural antioxidants afford protection against coronary heart disease, yet antioxidant supplementation trials have largely reported only marginal health benefits.
In view of the controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy inflavone therapy our research is focused on the molecular mechanisms underlying vascular protection (protection of blood vessels) by isoflavones. This project will provide insights into the cardiovascular benefits of dietary isoflavone supplementation.
Understanding the mechanisms of action of dietary soy isoflavone in human endothelial cells will provide valuable insights for clinicians and the pharmaceutical industry of potential alternative strategies for the treatment of postmenopausal woman and patients at risk of coronary heart disease.
University of Reading | £56,114
36 months project
Platelets are tiny blood cells that are responsible for triggering the blood to clot when tissues become injured, and therefore perform a vital protective function by preventing excessive bleeding. Platelets posses a wide range of specialised proteins and molecules that enable them to recognise damaged tissue and trigger an explosively fast response that culminates in the rapid formation of a blood clot. Platelets regulate their functions using complex control mechanisms. Unfortunately in certain disease states platelet function is activated inappropriately, leading to blood clot formation within blood vessels, or thrombosis. Thrombosis often occurs in coronary and carotid arteries, causing heart attacks and strokes, respectively. These two conditions are major causes of death and suffering in the UK.
This study has developed from the observation that certain drugs used to treat diabetes also reduce the risk of cardiovascular disease. Both researchers at the University of Reading and other researchers have established that the target of these drugs (a protein) is present in platelets, and that these drugs and natural substances in the body that interact with the protein may inhibit the function of platelets. This project may explain why these drugs reduce the risk of cardiovascular problems.
University of Bradford | £55,792
36 month project
Obesity is an increasing problem in the UK and is associated with the increased risk of diabetes, elevated blood pressure and heart disease. It is thought that a group of hormones, called adipokines, released from the fat stores in the body help to prevent heart disease. Obesity reduces the levels of adipokines in the blood. The reduction of blood adipokine levels is associated with increased risk of diabetes and heart disease. This project will test if one such adipokine, called adiponectin, can influence the activity of blood platelets. Blood platelets are a group of cells that form blood clots inside the blood vessels to cause thrombosis. The study will increase our understanding of how obesity is linked to increased heart disease and how these hormones protect our bodies from heart disease and thrombosis.
University of Glasgow | £84,904
24 month project
The heart is composed of millions of single heart muscle cells, which act in a synchronised way to enable the pump to contract and relax for the duration of ones life. The heart muscle receives nutrients via the coronary blood vessels to power the contractile activity. During coronary artery disease some of these vessels block and a region of the heart muscle is starved of nutrients. In severe cases this results in a heart attack, which can lead either to sudden death or a prolonged phase of poor heart function leading to a medical condition termed heart failure (HF). There is no cure for HF and very few drugs for treatment. This is due to a poor understanding of the mechanisms underlying the process of HF. The hearts ability to contract and relax is partly dependent upon a store of calcium (the sarcoplasmic reticulum- SR) located within the muscle cells. During HF, many patients have hearts which are unable to relax sufficiently. The reasons for this abnormality remain unclear. Numerous possibilities exist but one promising candidate is alteration of SR calcium handling. This proposal will investigate the specific alteration of SR calcium handling on whole heart pump function and heart muscle cells.
University of Leeds | £79,322
18 month project
Statins improve survival in patients with cardiovascular disease. It was originally thought that this was exclusively due to their ability to reduce cholesterol in the blood, which in turn prevents the development of plaques in the blood vessels that cause coronary artery disease and heart attacks. However, in recent years people have shown that statins have other beneficial actions, which could be very important for patients with cardiovascular disease. Researchers at the University of Leeds have a novel idea that statins could affect specialised areas (‘caveolae’) of the membrane of the heart muscle cell itself which would directly influence the way the heart responds to adrenaline. Caveolae are little pits in the membrane that are enriched in, and depend on, cholesterol. The researchers will investigate how treatment of heart muscle cells with the most commonly prescribed statin, simvastatin affects caveolae, and look in turn at how this controls the function of the cell. The data they already have suggests that this could be very important for improving the function of the heart, particularly in patients with heart failure.
