THE ROLE OF DIFFUSE MYOCARDIAL FIBROSIS IN MYOCARDIAL STIFFNESS
Funder
National Health and Medical Research Council
Funding Amount
$545,126.00
Summary
In many cardiac diseases stiffening of the heart can occur, resulting in worsening symptoms of breathlessness, fatigue and even death. Whilst the exact cause of heart stiffening is not well known, fibrosis of the heart is believed to of prime importance. This research will examine the contribution of fibrosis to heart stiffening, using cardiac magnetic resonance imaging (CMR) as a non-invasive means of assessing heart fibrosis.
“Beyond The Tape Measure” - Measuring The Impact Of Abnormal Flow Dynamics On Dilation Of The Ascending Aorta.
Funder
National Health and Medical Research Council
Funding Amount
$723,771.00
Summary
Dilation of the ascending aorta is an important cause of death, leading to aortic rupture and dissection. The rate of complications has not improved in two decades, because our ability to detect and predict disease has not changed. This project will use 4D flow and other types of cutting edge magnetic resonance imaging to address this clinical need, building knowledge regarding the abnormal flows that cause aortic dilatation, enabling earlier diagnosis and providing new insights.
Early Detection Of Chemotherapy-related Cardiotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$269,401.00
Summary
This project examines myocardial dysfunction in breast cancer patients treated with anthracycline chemotherapy. Chemotherapy related cardiotoxicity is often asymptomatic until significant cardiac dysfunction occurs. Cardiac function is evaluated by LV ejection fraction (LVEF), which is a coarse measure of cardiac function. Strain analysis measure myocardial deformation and is more sensitive to subclinical cardiac dysfunction, and demonstrates alterations prior to the development of reduced LVEF.
Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
CCR4/NOT Complex Is A Conserved Regulator Of Heart Function
Funder
National Health and Medical Research Council
Funding Amount
$467,567.00
Summary
Cardiovascular diseases kill an Australian every 11 minutes. The goal of this proposal is to characterize the role of the conserved heart regulators in cardiac function and disease. Our combined multi-species and informatics approach has identified a major disease locus for sudden cardiac death in humans, which we propose to characterize. This work can lead to new classes of drugs to improve cardiac health and also aid in early diagnosis of patients susceptible to sudden cardiac death.
Targeting Lipids Regulated In A Setting Of Physiological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$489,970.00
Summary
Existing heart failure therapies largely delay heart failure progression rather than reversing the disease. New therapeutic strategies with the ability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether lipids that are secreted by the heart in a setting of “good” physiological heart growth (as occurs with exercise) can be targeted to restore function of the failing heart.
New Gene Discovery In Familial Hypertrophic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$418,493.00
Summary
Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of pe ....Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of people with familial hypertrophic cardiomyopathy.Read moreRead less
Regulation Of Endogenous Heart Regeneration By An Anti-fibrotic MicroRNA.
Funder
National Health and Medical Research Council
Funding Amount
$440,949.00
Summary
In contrast to the adult heart, the newborn heart undergoes scarless healing following a heart attack. The molecular mechanisms that govern heart regeneration in newborn mammals are not fully understood. The goal of the current study is to determine the role of a recently identified family of molecules known as microRNAs in the regulation of scarless healing. We propose a novel strategy for re-activation of microRNAs in the adult heart to promote regeneration following heart attack.
Regulating Gene Expression Changes In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$690,754.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.