Fibrosis is a major mechanism driving chronic disease. A specific pathologic process (TGF/Smad signalling) plays an important role in scarring of the kidney and the heart; but our understanding of this process is limited. Our exciting new data has identified a chemical modification of a component of this scarring pathway (acetylation of Smad3), and this project seeks to determine whether this modification plays a pivotal role in regulating tissue scarring.
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.
Preclinical Relaxin Therapy To Reverse Cardiac Fibrosis And Gain Functional Benefits
Funder
National Health and Medical Research Council
Funding Amount
$724,754.00
Summary
Cardiac fibrosis is a key factor promoting heart disease and onset of complications including arrhythmias and heart failure. There is urgent and unmet need of drugs that can reverse fibrosis. By documenting anti-fibrotic action of a peptide hormone relaxin, CIA and his team will test therapeutic effect of relaxin in heart disease models focusing on fibrosis-reversal and functional gain, particularly arrhythmias. This work would promote development of relaxin as a new cardiovascular drug.
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.
Fibrosis is a common feature of many forms of heart disease. Despite the recognised central role of reactive oxygen species (ROS) in cardiac fibrosis, antioxidant approaches have failed in clinical trials. We have discovered a new mechanism for ROS-mediated fibrosis that is depleted in human heart failure, and will test an innovative therapeutic approach that is imminently translatable given the development by members of our team of a specific peptide blocker effective in blocking this pathway.
Regulatory T Cells And Cardiac Fibrosis In Hypertensive Heart Disease: Cellular And Molecular Mechanisms Of Suppression
Funder
National Health and Medical Research Council
Funding Amount
$715,316.00
Summary
Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflam ....Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflammation.Read moreRead less
Novel Aspects Of The Renin Angiotensin System In Cardio-renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$497,330.00
Summary
Cardiovascular disease and chronic kidney disease are major public health problems with increasing incidence and prevalence in Australia. There are complex causal relationships between these diseases, and each of them may be caused by or be a complication of the other. This proposal will investigate the role of an important hormone system, the renin angiotensin system, in experimental models and in patients with heart and kidney disease. The results may identify novel markers in the blood that c ....Cardiovascular disease and chronic kidney disease are major public health problems with increasing incidence and prevalence in Australia. There are complex causal relationships between these diseases, and each of them may be caused by or be a complication of the other. This proposal will investigate the role of an important hormone system, the renin angiotensin system, in experimental models and in patients with heart and kidney disease. The results may identify novel markers in the blood that can predict if someone will develop kidney disease.Read moreRead less
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.
Identifying Donor And Recipient Gene Pathways In Renal Transplant Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,082,069.00
Summary
We have identified a 13 gene set that predicts renal transplant fibrosis and graft loss in patients. Interestingly some of these gene are donor as well as recipient related. In this project we aim to investigate these gene pathways in cell lines and animal models to better understand how the cause of renal fibrosis after transplantation.