Preventing Myocardial Infarction: A Mouse Model Of Atherosclerotic Plaque Instability/rupture As Unique Tool For Establishing Novel Pharmacological Strategies And Targeted Molecular Imaging
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarctio ....Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarction.Read moreRead less
Novel Selective Anti-platelet And Clot-specific Anticoagulant Strategies Targeting Conformational States Of GPIIb/IIIa
Funder
National Health and Medical Research Council
Funding Amount
$496,517.00
Summary
The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding compl ....The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding complications are also a major financal burden for our health care system. Thus, progress towards therapeutic strategies with less bleeding complications is highly sought-after. The proposed project aims to generate new antibody-based agents for platelet inhibition. One group of these agents do only block platelets when they are activated. Furthermore, these agents allow an enrichment of potent inhibitors of coagulation factors at the site of the clot. Thus, these inhibitors should predominatly act at the site where they are needed. At the same time the overall concentration of inhibitors of coagulation factors can be kept low and the functions of non-activated platelet can be left intact. Overall, the proposed project aims for the development of novel anti-platelet and anticoagulant strategies with high anti-thrombotic efficacy and low bleeding risks.Read moreRead less
Structural And Functional Studies On The Interaction Between Alpha2-Antiplasmin And Plasmin
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Fibrinolysis is the process by which the body dissolves clots. In this proposal we aim to investigate how the fibrinolysis inhibitor alpha2-antiplasmin interacts with the clot dissolving protease enzyme plasmin. These data will be useful for developing new approaches to accelerate plasmin-mediated clot breakdown.
Investigation Of A New Platelet Contractile Mechanism Regulating Thrombus Stability
Funder
National Health and Medical Research Council
Funding Amount
$499,670.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found a new contraction process that causes tight packing of platelets in a clot, enabling the clot to avoid detachment under blood flow. We will study this process and explore the possibility that its inhibition may provide a new way in which to loosen clots, promoting their removal. These studies will provide new insight into clot stability, and may provide clinical benefit in the delivery of clot dissolving agents .
An International Randomised Trial Of Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (INSPIRE)
Funder
National Health and Medical Research Council
Funding Amount
$1,989,986.00
Summary
Patients who develop venous blood clots or pulmonary embolism, without an underyling cause, are at very high risk of recurrence once anticoagulant treatment (warfarin) is discontinued. The international INSPIRE trial is assessing whether low-dose aspirin treatment (a simple and cheap alternative to warfarin) is effective and safe in preventing further blood clots. If proven effective, aspirin could potentially prevent thousands of patients worldwide from experiencing such events.
Low-dose Aspirin To Prevent Recurrent Venous Thromboembolism (ASPIRE) Study: A Multicentre Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,108,600.00
Summary
In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to pr ....In approximately one-third of patients who develop deep vein thrombosis or pulmonary embolism, this event is 'unprovoked' . These patients are at very high risk of recurrence once treatment with warfarin is discontinued. Warfarin treatment is very effective to prevent recurrence but is inconvenient because it has to be very closely monitored with blood tests and also causes serious bleeding complications in a significant number of patients. There are currently no other treatments available to prevent recurrent thrombosis. Low-dose aspirin treatment offers a simple, inexpensive, and widely practicable alternative to warfarin but has not yet been proven to be effective for preventing recurrent thrombosis. This study will investigate the effectiveness and safety of aspirin to prevent recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism who have completed standard anticoagulation with heparin and warfarin. If proven to be effective, aspirin could potentially prevent thousands of patients from experiencing recurrent venous thromboembolism or fatal pulmonary embolism worldwide and also save millions of dollars in health care costs each year.Read moreRead less
Investigation Of Activating Signals Transmitted During Platelet Aggregation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies a ....The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate platelet-platelet interactions during the course of blood clot formation, since this is an important determinant not only of normal clot formation, but also in the development of harmful blood clots (thrombi) associated with the onset of diseases such as heart attack and stroke. Our particular focus is on the way in which platelets communicate to one another during the course of platelet thrombus development. Particulary, we are interested in the role of calcium as a signal mediating platelet-platelet communication. We believe that the transmission of these calcium signals may be the key signaling mediator of blood clot formation and normal haemostasis.Read moreRead less
Investigation Of The Role For GPVI In Platelet Function And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$542,772.00
Summary
Blood cells play an important role in maintaining healthy blood vessels. We are studying the role of platelets in blood clots following vessel injury. However, while critical for normal blood vessel maintenance, these cells also contribute to diseases including thrombosis. We will examine how an important platelet receptor called GPVI promotes blood clot formation, and examine whether combining anticoagulant drugs with GPVI deficient platelets leads to a more effective anticlotting approach.
Investigation Of A Novel Role For Factor XIII In Regulating The Adhesive Function Of Platelets
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
Platelets are small specialised blood cells that are extremely important for the normal formation of blood clots and for the repair of injured blood vessels. We are studying the processes that allow platelets to stick to the site of vessel injury and to each other to form stable blood clots. If this process proceeds unchecked, harmful blood clots can form which block blood vessels and cause heart attacks and strokes. There are many factors, both inside and outside platelets, which control how bi ....Platelets are small specialised blood cells that are extremely important for the normal formation of blood clots and for the repair of injured blood vessels. We are studying the processes that allow platelets to stick to the site of vessel injury and to each other to form stable blood clots. If this process proceeds unchecked, harmful blood clots can form which block blood vessels and cause heart attacks and strokes. There are many factors, both inside and outside platelets, which control how big and how fast a blood clot grows and whether it becomes harmful enough to cause a blood vessel blockage. One of these factors is the level of platelet 'stickiness' or 'reactivity'. We are working towards a better understanding of how platelet reactivity is regulated. Specifically, we believe we have identified a new factor which keeps blood clots at a size that is not harmful to cause blood vessel blockade. This information will not only increase our knowledge of blood clot formation in health and disease but also may help in the development of new therapies for the prevention of heart attack and stroke.Read moreRead less
Molecular Analysis Of Myelodysplasia In The Nup98HoxD13 Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$351,502.00
Summary
Myelodysplastic syndrome is a preleukemic condition which is poorly understood and occuring at an increasing frequency. Unfortunately no targeted therapy exists. Two features of the disease are abnormal gene expression and abnormal cell death. We have a uniquely accurate model of this disease, and we plan to use it to investigate these two phenomena which will lead to greater understanding of the disease and new molecular targets for therapeutic agents to be developed and tested in our model.