Identification Of A Novel Adhesion Mechanism Regulating Platelet-endothelial Interactions.
Funder
National Health and Medical Research Council
Funding Amount
$501,691.00
Summary
Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflamma ....Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflammatory disease.Read moreRead less
Understanding The Role Of Cell Death In Blood Vessel Regression And Regrowth
Funder
National Health and Medical Research Council
Funding Amount
$468,059.00
Summary
Blood vessels are essential to distribute oxygen and nutrients throughout our bodies, and as such, disruptions to normal blood vessel behaviour can have significant impacts on health. This research is aimed at understanding how blood vessel networks can regrow after damage in order to maintain healthy blood supply to a tissue. This work will be particularly relevant to diseases where blood vessel loss or inappropriate blood vessel growth occur.
How Is Lipoprotein Disposition Influenced By Fenestrae In The Hepatic Sinusoidal Endothelium?
Funder
National Health and Medical Research Council
Funding Amount
$310,500.00
Summary
Understanding lipoprotein metabolism is critical for the prevention of vascular disease. The liver is the main site for lipoprotein metabolism. The initial step in the metabolism of lipoproteins by the liver is their transfer across the liver sinusoidal endothelial cells from the blood to the liver cells. Sinusoidal endothelial cells contain pores called fenestrae that are thought to allow direct passage of large substances and thus filter lipoproteins on the basis of size. We propose to fully d ....Understanding lipoprotein metabolism is critical for the prevention of vascular disease. The liver is the main site for lipoprotein metabolism. The initial step in the metabolism of lipoproteins by the liver is their transfer across the liver sinusoidal endothelial cells from the blood to the liver cells. Sinusoidal endothelial cells contain pores called fenestrae that are thought to allow direct passage of large substances and thus filter lipoproteins on the basis of size. We propose to fully define the role of fenestrae in the ultrafiltration of particles such as lipoproteins and microspheres. This will confirm that ultrafiltration by fenestrae in the liver endothelium is an important biological process akin to filtration by the kidney, and relevant for lipoprotein metabolism. We will determine whether oxidative stress, which generates large gaps in the sinusoidal endothelium, increases the transfer of lipoproteins into the liver. This provides a novel mechanism for fatty liver that follows toxic liver injury, and hence, a therapeutic target for this condition. We will determine whether loss of fenestrae induced by the synthetic non-ionic surfactant, pluronic 407, reduces transfer of lipoproteins. This is an entirely novel mechanism and risk factor for hyperlipidaemia. Finally we will investigate lipoprotein (a) which is a potent risk factor for vascular disease. We will assess with lipoprotein (a), through binding other lipoproteins and increasing their size, impedes their transfer through the fenestrations for subsequent hepatic metabolism. From the basic perspective, these studies will prove that fenestrations in the liver endothelial cell are an ultrafiltration system that is significant for lipoprotein metabolism. From the clinical perspective, the studies will generate novel mechanisms for impaired hepatic metabolism of lipoproteins as well as indicating that fenestrae are a potential target for the development of lipid-lowering pharmacotherapies.Read moreRead less
Factor XII Dependent Coagulation, Thrombin And Platelet Glycoprotein 1ba In Arterial Thrombosis And Bleeding Disorders
Funder
National Health and Medical Research Council
Funding Amount
$104,664.00
Summary
Clot formation is the key event underlying heart attacks and strokes. There is new data that Factor XII (FXII) can play an important role in clot formation-thrombosis. We aim to examine the role FXII plays in clot formation, in particular the role of FXII in thrombin generation, which is the central event of clot formation, and its interaction with platelet glycoprotein 1ba (another important molecule in thrombosis). New insights into clotting and new therapies can result from our research.
Normal organ development and many disease processes, such as cancer and tissue damage, depend upon formation of new blood vessels. Our research seeks to identify novel factors regulating blood vessel growth. In this context we have examined the role of proteins that mediate communication between cells, called connexins. By increasing our understanding of the factors affecting blood vessel growth we learn how to create novel therapies to enhance the treatment of ischemic disease and cancer.
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.