Investigation Of A New Approach To Regulate Fibrin Clot Retraction And Arterial Thrombolysis
Funder
National Health and Medical Research Council
Funding Amount
$483,171.00
Summary
Pathological blood clots are removed in patients by administering clot dissolving drugs (fibrinolytics). However these drugs are quite often ineffective and cause bleeding. We have identified a new platelet-mediated pathway controlling contraction of blood clots, important for clot stability. In this proposal, we will examine the potential for inhibitors of this pathway to loosen blood clots, and facilitate the actions of fibrinolytics to promote clot dissolution.
Intravascular Leukocyte Trafficking During Thromboinflammation
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Unblocking blood vessels to treat heart attack and stroke can unfortunately cause a paradoxical worsening of organ damage, due to increased inflammation upon blood flow restoration. We have identified a novel way in which this side-effect is regulated by the small blood clotting cells platelets, and the protein fibrin. We will investigate ways to reduce the pro-inflammatory role for platelets, and define safer clot busting treatments.
To Determine The Means By Which Plasminogen Activators Modulate Integrity Of The Blood Brain Barrier
Funder
National Health and Medical Research Council
Funding Amount
$523,084.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. However, t-PA can also cause brain injury and influence the blood brain barrier (BBB) which has implications for the treatment of patients with ischaemic stroke. This project will use in vitro and in vivo models to understand the mechanism by which t-PA modulates the BBB. A novel tPA variant will also be created that ultimately may be of benefit for patients with ischaemic stroke.
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 .