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Coronary Atherosclerosis And Its Relationship With Platelet Activation
Funder
National Health and Medical Research Council
Funding Amount
$101,039.00
Summary
Blood clots are critical to the development of heart attacks, which kill many thousands of Australians annually. Platelets are cells in the blood that play an essential role in formation of blood clots, and coronary disease is associated with platelet activation. This research study will investigate the nature of platelet activation in the arteries of the human heart, its relationship to activation of inflammatory cells, and to the severity of narrowings in the arteries of the human heart.
HMGB1, A Cytokine Linking Inflammation, Lipid Accumulation, And Platelet Activation In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
Atherosclerosis, or hardening of large arteries is the underlying cause of up to 50% of deaths in Western communities, primarily from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the accumulation of fats such as cholesterol into the inner lining of blood vessels including those supplying vital organs such as the heart and brain. This study focuses on understanding how a major inflammatory factor, HMGB1, influences this disease process.
Platelet-Activating And Proinflammatory Effects Of Proteins Secreted By Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$515,986.00
Summary
Skin or other Staphylococcus aureus (SA, golden Staph.) infections are common in Aboriginal Australians. We address the question whether atherosclerotic disease is accelerated by this bacterial infection. We will investigate whether a class of newly described toxins secreted by SA activates blood cells and leads to clot formation and potentially heart attack. We will evaluate plasma samples from cardiac patients and Aboriginal Austr. and will develop and test therapeutics in vitro and in mice.
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Atherothrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$674,880.00
Summary
CRP is a plasma marker that can identify individuals at high risk for heart attack and stroke. Our preliminary data suggests that plasma CRP is not only an innocent marker, but can also be activated and thereby become a strong inflammatory stimulus by changing from a five unit to a single unit form on the surface of activated platelets. We will investigate this CRP activation in vitro, in animal models and in patients, and aim to develop new drug therapies for diseases such as heart attack.
Novel Single-chain Antibody-targeted Nanoparticles For Diagnosis Of Vascular Diseases In Magnetic Resonance Imaging
Funder
National Health and Medical Research Council
Funding Amount
$460,797.00
Summary
The aim of this project is to develop targeted imaging agents that seek out specific markers for various states of cardiovascular disease. These agents would provide a method for detecting the presence and level of atherosclerosis and thrombotic events. The targeted nanoparticles may provide a unique opportunity to detect very early plaques, the vulnerability of existing plaques and difficult to diagnose vessel blockages such as pulmonary embolism.
MYOCARDIAL NEOVASCULARIZATION FOR ISCHEMIC HEART DISEASE USING BONE MARROW-DERIVED ANGIOBLASTS
Funder
National Health and Medical Research Council
Funding Amount
$577,400.00
Summary
Congestive heart failure remains a major public health problem. In Western societies heart failure is primarily the consequence of a previous myocardial infarction. We have recently identified certain cells in the bone marrow of adult humans that can cause new blood vessel development in the heart after infarction, protecting the heart muscle cells against death and preventing heart failure. Since the cardiovascular diseases that are most likely to benefit from treatments utilizing adult bone ma ....Congestive heart failure remains a major public health problem. In Western societies heart failure is primarily the consequence of a previous myocardial infarction. We have recently identified certain cells in the bone marrow of adult humans that can cause new blood vessel development in the heart after infarction, protecting the heart muscle cells against death and preventing heart failure. Since the cardiovascular diseases that are most likely to benefit from treatments utilizing adult bone marrow-derived endothelial progenitors, or angioblasts, predominantly affect aging individuals, critical questions that must be addressed are whether advanced age and-or progression of cardiovascular disease reduce the total numbers and-or the functional activity of such cells. In the current proposal we will investigate the relationship between increasing age or progression of ischemic heart disease and changes in the number and in vivo biologic properties of human angioblasts. Patients at various ages and stage of cardiovascular disease will be studied. Angioblast numbers will be quantitated in freshly obtained bone marrow cells. The ability of purified angioblasts to be targeted to the ischemic heart will be studied by labeling the angioblasts with a radioactive tracer and measuring tracer uptake in the heart at various time points after intravenous infusion of the cells. Finally, angioblast functional capacity will be evaluated using standard measurements of heart function before and at various time points after reinfusion of cells into the donor. In Aims 2 and 3 of this proposal we will focus our investigations on the potential use of angioblast therapy for reversal of established chronic heart failure in our animal models. Specifically, we will investigate whether induction of neovascularization results in cardiomyocyte regeneration and explore novel strategies to augment heart muscle regeneration by increasing angioblast trafficking to the damaged myocardium .Read moreRead less