A Temporal Profile Of Signaling Via Phosphorylation During Myocardial Ischemia - Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$369,641.00
Summary
Cardiovascular disease (CVD) is the major cause of death in Australians and sequelae post-myocardial ischemia - reperfusion (I-R) are responsible for the greatest proportion of CVD-related mortality. Despite this burden, there is little known of the molecular events that mediate I-R. This project will utilize cutting-edge technology to elucidate the molecular signaling events that lead to I-R injury, as well as determine the basis for protection afforded by clinical pre- and post-conditioning.
Role Of Urotensin II, A Novel Vasoconstrictor Factor, In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Urotensin II (UII) is a newly discovered peptide that may play an important role in human health and disease. It has been found to be a potent constrictor (narrower) of blood vessels and therefore may be involved in diseases such as hypertension (high blood pressure) and heart failure (weak heart muscle disease). Furthermore, many other factors that constrict blood vessels have also been found to have effects on key organs, such as the heart. Our preliminary data suggests that this is also true ....Urotensin II (UII) is a newly discovered peptide that may play an important role in human health and disease. It has been found to be a potent constrictor (narrower) of blood vessels and therefore may be involved in diseases such as hypertension (high blood pressure) and heart failure (weak heart muscle disease). Furthermore, many other factors that constrict blood vessels have also been found to have effects on key organs, such as the heart. Our preliminary data suggests that this is also true of urotensin II. The proposal studies seek to determine the role of urotensin II in the : (i) periphery, by assessing contraction of forearm vessels to low doses of UII in normal volunteer subjects and patients with hypertension and heart failure; (ii) heart, by measuring expression of UII and its receptor in normal and failing human heart tissue; the UII response to experimental heart attack in the rat and in cell culture of important heart cells; (iii) general circulation, by measuring plasma levels in health and disease. The significance of this project is that if it is found that UII plays an important role in these diseases, then agents that block this system may represent a major therapeutic advance in the management of these diseases.Read moreRead less
Therapeutic Silencing Of Egr-1 By Novel Catalytic Oligodeoxynucleotides For The Treatment Of Acute Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$384,353.00
Summary
Heart attack remains a major health problem. We have identified a gene in the heart which is turned on in the first few hours of a heart attack. We have shown in principle that switching this gene off using a novel synthetic drug, reduces heart attack size. Our project assesses the long term effects of this drug on the heart using state of the art imaging when the the drug is administered in a clinically relevant manner. This study may faciliate a new treatment approach for this condition.
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.
Role Of Advanced Glycated End Products In Mediating Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$414,000.00
Summary
Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attach ....Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attached proteins (AGEs) into mice to see how they directly influence the vessel wall. We will characterise molecular and cellular changes in response to these AGEs. These studies will ultimately lead to better treatments to prevent, slow down or reverse blood vessel damage in diabetes.Read moreRead less
Examining Genome Wide Gene Expression Changes During Cardiac Injury And Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
Heart attacks are the leading cause of death in Australia. Following a heart attack, the loss of beating heart cells is replaced with a permanent scar and this limits the heart from functioning properly. The zebrafish can uniquely recover from a heart attack. New heart cells are generated rather than scar formation. This project will use the zebrafish to identify new signals that promote heart regeneration and can potentially be applied in human hearts to reverse the damage following injury.
Aliskiren: Cardioprotection By Increased Bradykinin Levels?
Funder
National Health and Medical Research Council
Funding Amount
$295,236.00
Summary
Aliskiren is a new treatment for hypertension. Our recent studies indicate that aliskiren may have additional benefits for patients with ischaemic heart disease and heart failure. This research project will investigate the effects of aliskiren in different forms of heart disease in rats, in order to provide information that will help patients obtain the maximum benefit from this treatment.
Restoring Microcirculatory Perfusion In ST-elevation Myocardial Infarction: The RESTORE MI Study
Funder
National Health and Medical Research Council
Funding Amount
$3,274,537.00
Summary
Current heart attack treatments have focussed on re-opening the blocked coronary artery but despite this, many patients still suffer significant heart damage because of inadequate blood flow to the heart muscle due to damage to the small blood vessels - the microcirculation. This study seeks to identify heart attack patients with damage to the microcirculation and will conduct a randomised trial of clot busting medications to reduce microcirculation damage and to improve heart function.