The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives ....The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives given the prevalence and severity of disease.Read moreRead less
Optimising Efficacy Of A Peptide Derived Against The Alpha-interacting Domain Of The L-type Calcium Channel In Reduction Of Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$405,063.00
Summary
A heart attack is associated with an increase in free radicals and calcium in heart muscle cells. The function of the L-type calcium channel, a protein responsible for calcium entry into cells, is altered by free radicals and this contributes to the development of heart disease. We now have considerable proof of concept that a peptide derived against the L-type calcium channel can decrease heart injury. We will optimise efficacy and delivery of the peptide to prevent heart failure.
METABOLOMIC INSIGHTS INTO THE PATHOGENESIS AND RISK ASSESSMENT OF UNSTABLE CORONARY ARTERY DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$876,896.00
Summary
Atherosclerosis (AS) is the single most common cause of cardiovascular disease and is the major contributor to the development of angina, heart attacks, coronary heart disease and stroke. Early identification and characterisation of the disease, is critical for effective treatment. In this project we will develop a new test to identify those individuals with unstable disease that are at greatest risk of a coronary event (heart attack).
Manipulation Of Intracellular Arginine Content In Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$476,264.00
Summary
The lining layer of blood vessels (termed the 'endothelium') plays a vital role in the control of blood vessel function. Recently it has been shown that risk factors for heart and vascular disease (smoking, high blood pressure, high cholesterol and diabetes), heart attack and heart failure are associated with an abnormally functioning endothelium. In particular, the endothelium maintains blood vessels in a relaxed state, prevents the formation of blood clots (which may cause heart attack and str ....The lining layer of blood vessels (termed the 'endothelium') plays a vital role in the control of blood vessel function. Recently it has been shown that risk factors for heart and vascular disease (smoking, high blood pressure, high cholesterol and diabetes), heart attack and heart failure are associated with an abnormally functioning endothelium. In particular, the endothelium maintains blood vessels in a relaxed state, prevents the formation of blood clots (which may cause heart attack and stroke) and prevents the thickening of blood vessels. These important actions of the endothelium are explained by the production of nitric oxide (NO) a small chemical messenger that is derived from an amino acid, L-arginine, which circulates in blood. The amount of NO produced by endothelial cells is very dependent on the amount of arginine available, and this is determined by a careful balance between the amount of arginine taken (transported) into cells and the amount that is destroyed (metabolized) by an enzyme called arginase. Research undertaken in our laboratory is directed at understanding the important balance between arginine transport and arginase activity, as a basis for identifying new ways to prevent and treat cardiovascular disease. The current proposal describes a series of studies which will critically examine the importance of arginine transport and arginase activity, using transgenic models of over-activity and under-activity of these systems. Once established we will test the possibility that manipulating these systems may prevent atherosclerosis.Read moreRead less
Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients sufferi ....Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients suffering heart attack.Read moreRead less
Microvascular Function And Outcome In Patients With Acute Coronary Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Damage to the small vessels of the heart is a hallmark of heart attacks. Furthermore, small vessel dysfunction (MVD) is associated with a worse prognosis even in the presence of an unblocked major coronary artery following a heart attack. Using novel invasive assessments, we aim to analyse the prevalence and clinical predictors of MVD, assess the impact of MVD on short and long-term outcome after heart attack and address the impact of new treatments on MVD and heart muscle recovery.
Platelet Receptor Shedding In Stroke And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$552,503.00
Summary
In response to tissue injury and bleeding, blood platelets use receptors to form a thrombus (blood clot) and block further loss of blood and aid tissue repair. In inflammation or disease, abberant platelet activation can form a thrombus within cerebral (stroke) or coronary vessels (heart attack). We examine how a thrombus-limiting step (platelet receptor shedding) is triggered in thrombus-forming platelets, and if shed receptor can be used as a blood marker of abberant platelet activation.
Cardiovascular disease is the leading cause of death in Australia. Aliskiren is the first renin inhibitor-type drug to be approved for clinical use for treatment of hypertension. The aim of this project is to evaluate the effectiveness of aliskiren for the treatment of heart attack and heart failure, as compared to existing therapies. Aliskiren may potentially replace or complement current therapies, thereby reducing death and improving health and economic benefits for the community.
Development Of A Sensitive Point Of Care Diagnostic Assay For Troponin I
Funder
National Health and Medical Research Council
Funding Amount
$137,650.00
Summary
This research aims to develop a diagnostic for immediate monitoring of patients presenting with chest pain, with the presumption of heart attack. The novel diagnostic platform will enable the estimation of a key indicator of heart muscle damage to be performed within a ten to fifteen minute window. This will aid speedier diagnosis and propoer triage of patients presenting with chest pain.
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.