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Role Of Microparticles In Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Interventional cardiology has reduced the mortality rate associated with heart attack, unfortunately the prevalence of heart failure has subsequently increased, caused in part by reperfusion injury of previously occluded vessels. We aim to identify novel insights into the pathogenesis of IR injury in the heart, as well as the development of new approaches to prevent cardiac damage during cardiac surgery, transplantation, post-angioplasty and coronary artery stenting.
The Role Of Aquaporins In Cardiac Ischaemia And Reperfusion
Funder
National Health and Medical Research Council
Funding Amount
$412,670.00
Summary
We are studying the important clinical problem of why the heart doesn't work very well after it has been deprived of blood. This may occur during a heart attack due to coronary artery disease and during cardiac surgery when the heart is stopped. The problem affects children as well as adults undergoing surgery. The reason the heart doesn't work well is related to energy supply and tissue damage caused during the shortage of blood supply and the period soon after flow is restored. Until the heart ....We are studying the important clinical problem of why the heart doesn't work very well after it has been deprived of blood. This may occur during a heart attack due to coronary artery disease and during cardiac surgery when the heart is stopped. The problem affects children as well as adults undergoing surgery. The reason the heart doesn't work well is related to energy supply and tissue damage caused during the shortage of blood supply and the period soon after flow is restored. Until the heart recovers, inadequate pump function may cause low blood flow problems downstream in vital organs such as the brain and kidneys. Under the microscope, a common feature of affected hearts is swelling of the cells and of the energy producing parts called mitochondria. We have identified, for the first time, unique proteins that allow water to move into and around cells of the heart. These proteins are called 'aquaporins' and early results suggest they are involved in how mitochondria deal with a shortage of blood supply. Interestingly, aquaporins are also affected in diseases that affect muscle strength, and we are using what is known in these diseases to further study the role of aquaporins in the heart. Our experiments to will test heart function from the level of the cell, all the way up to the whole heart. To improve the power of our experiments, we are working with mice that lack the special water transport proteins, as a prelude to developing drug therapy for this important problem. By manipulating aquaporin levels or function, we plan to improve heart preservation during periods of no blood flow, and after surgery. This would importantly reduce the risks associated with heart attack and cardiac surgery by avoiding complications associated with poor pump function.Read moreRead less
Activated Platelets As Unique Targets For Early Imaging And Site-directed Therapy Of Cardiovascular And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$846,979.00
Summary
Heart attack and inflammatory diseases such as rheumatoid arthritis und multiple sclerosis either kill or severely disable people. We use the presence of platelets early on in these diseases to develop methods for early diagnosis as well as potential drugs for site-directed therapy. We have developed new biotechnological tools to perform novel high sensitivity imaging in Positron Emission Tomography (PET) and laser light imaging as well as a localised anti-inflammatory therapy.
Remote Ischaemic Preconditioning And Its Effect On Coronary Physiology And Platelet And Leukocyte Activation.
Funder
National Health and Medical Research Council
Funding Amount
$124,608.00
Summary
Remote ischaemic preconditioning (RIPC) is a novel treatment which can improve patient outcomes after a heart attack, undergoing coronary stenting or bypass surgery. The mechanisms by which RIPC confers this cardio-protection is not clear. We will study the effects of RIPC on platelet activity and the flow of blood in the arteries that supply the heart. Understanding RIPC may open new avenues for treatment of patients with coronary artery disease, one of the major causes of death in Australia.
Novel Small Molecule FosB/AP-1 Inhibitors For The Prevention Of Proliferative Vascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$343,597.00
Summary
This project examines the effect of a novel FosB/AP-1 inhibitor (LK001) on neointima formation after injury in animal models of restenosis, atherosclerosis and abdominal aortic aneurysm, and a human ex vivo model of graft stenosis Given the current prevalence of CVD in Australia and the increasing demographic of susceptible individuals in the ageing population, this project has enormous clinical implications.
The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment o ....The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment of heart attack and stroke. The currently available drugs are not universally effective and their use is often limited by adverse reactions. In this submission, we propose to investigate the efficiency of a new drug that will prevent clot formation and will also tackle inflammation. This drug is a derivative of an enzyme that is already present on platelets and cells that line blood vessels. We have modified this enzyme in a manner that will increase the enzyme activity on the surface of platelets and on the cells that line the blood vessel wall. We will thoroughly study this new drug by performing experiments in the laboratory as well as by studying its effect in mice.Read moreRead less
Annexin-A1 Agonists Rescue Cardiac Contractile Function After Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$621,419.00
Summary
Myocardial infarction (or heart attack, a result of reduced coronary blood flow) and subsequent heart failure are the major cause of death in Western societies; this is expanding to all corners of the globe. New treatments for heart attack are thus essential. We have discovered that the natural hormone annexin-A1 rescues heart muscle function over the short-term, and propose that drugs based on annexin-A1 will prevent cardiac dysfunction of heart muscle up to several weeks after heart attack.
Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients sufferi ....Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients suffering heart attack.Read moreRead less