Assessing Efficacy Of Polyfunctional Nanoparticles Engineered For The Delivery Of Multiple Therapeutics In Reduction Of Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$317,678.00
Summary
A reduction in heart muscle damage after a heart attack is associated with a reduction in heart failure and an increase in life expectancy. However to date many therapeutic agents are not successful at reducing muscle damage because of difficulty in delivering the drugs to the target site. This project will address these delivery issues by making use of multifunctional nanoparticles which will allow for targeted delivery and release of therapeutics directly to damaged tissue following injury.
Adenosine A1 And A3 Receptor Mediated Cardioprotection In Ischaemic Myocardium
Funder
National Health and Medical Research Council
Funding Amount
$265,698.00
Summary
Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, ....Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, and continue to be, developed to reduce the extent of tissue damage and minimise prolonged reductions in heart function. The success of these interventions has been mixed. This research project takes the novel approach of identifying the true roles of two receptors present in the heart (the adenosine A1 and A3 receptors) which may play a crucial role in enhancing tolerance of the heart to disease and injury. We currently do not fully understand the roles of these receptors, although preliminary findings suggest they can exert powerful protective effects during disease conditions. From a fundamental viewpoint, identifying the roles of these two receptors will significantly advance our understanding of the mechanisms of injury and protection in the heart. From a therapeutic viewpoint, this study will take us closer to the potential use of adenosine receptor-based therapy in protecting the heart from ischaemic injury.Read moreRead less
Identification Of A New Thrombosis Mechanism Triggered By Dying Platelets
Funder
National Health and Medical Research Council
Funding Amount
$608,742.00
Summary
A severe reduction in blood flow (ischemia) to the intestines can trigger blood clot formation (thrombosis) in multiple organs, including the lungs. We have identified a new thrombosis mechanism that is triggered by the clumping of white blood cells in the intestines, leading to widespread thrombosis in the lung. Here we will investigate the mechanisms triggering this thrombosis mechanism with the ultimate aim of identifying more effective antithrombotic approaches.
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.
Improving Kidney Transplant Outcomes Using Normothermic Machine Perfusion
Funder
National Health and Medical Research Council
Funding Amount
$778,232.00
Summary
Kidneys donated for transplantation are at risk of damage that prevent the organ from working and reduce its lifespan. Normothermic machine perfusion is a device that can circulate oxygenated blood at normal body temperature through a donor kidney prior to transplantation. In doing so it is able to resuscitate the kidney and prevent injury. We will determine how machine perfusion achieves this remarkable effect and investigate new treatments for kidney injury.
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.
VCAM-targeted Delivery Of Recombinant CD39 To The Endothelium Is Antithrombotic, Antiinflammatory And Ameliorates Ischaemia Reperfusion Injury.
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Blockage of arteries with clots leads to heart attacks and strokes. Reestablishment of blood supply by clot-busting drugs or mechanical interventions paradoxically causes further organ injury. This is due to toxic chemicals generated by inflammatory processes and free oxygen radicals. We have created an unique drug that selectively targets blood vessels that are injured by process. The drug will deliver blood-thinning activity and reduce inflammatory stress selectively at the site of need.