Identification Of A MicroRNA-based Therapy For The Diabetic Heart
Funder
National Health and Medical Research Council
Funding Amount
$527,723.00
Summary
The incidence of diabetes is rising globally. The heart undergoes adverse remodelling in a setting of type 1 and 2 diabetes (diabetic heart/ diabetic cardiomyopathy) and this is associated with an increased risk for developing heart failure. New therapies for the diabetic heart are greatly needed. In this project we aim to identify and develop a novel therapy for the diabetic heart.
STudy Of Risk Assessment To Reduce Complications In Patients Following Noncardiac SurgerY (STRATIFY)
Funder
National Health and Medical Research Council
Funding Amount
$436,000.00
Summary
Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduce ....Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduces longterm risk. However, in many patients undergoing major noncardiac surgery, this approach may be inappropriately aggressive, as these patients are often elderly, have other diseases that make heart operations more difficult and risky than usual, and in any case may have a reduced life expectancy from the disease necessitating the operation. As the most critical issue is to ensure that patients undergo their surgery uneventfully, an alternative is the use of intensive medical therapy to protect the heart. This multicentre study, based at Brisbane hospitals that perform large numbers of major operations, will follow up patients for complications, and outcome (including quality of life) will be assessed six months after the operation. We will address two important questions about the efficacy and cost of risk reduction strategies. First, in patients at higher levels of risk and with a positive stress test, could a combination of medical therapy designed to protect the heart be as effective as current approaches, which include the performance of bypass surgery or coronary balloon angioplasty? Second, in patients identified as being at some risk - but low risk - are drugs sufficiently effective to avoid the need for further testing to quantify risk? As the population continues to age, the numbers of at risk patients undergoing major surgery will increase, and answers to these questions will provide important information to guide their management.Read moreRead less
Giving An Adult Life After Fontan Surgery To Those With The Most Severe Congenital Heart Conditions
Funder
National Health and Medical Research Council
Funding Amount
$1,295,355.00
Summary
The Fontan operation is the last of a series of operations performed for babies born with a single pumping heart chamber (ventricle). In the largest research of its kind, the Australia and New Zealand Fontan Registry partners with Heartkids, the parents’ association and the National Heart Foundation are intending to improve their life as they step into adulthood. We believe that our new standardised model of care will decrease their risk of experiencing adverse events such as stroke and reoperat ....The Fontan operation is the last of a series of operations performed for babies born with a single pumping heart chamber (ventricle). In the largest research of its kind, the Australia and New Zealand Fontan Registry partners with Heartkids, the parents’ association and the National Heart Foundation are intending to improve their life as they step into adulthood. We believe that our new standardised model of care will decrease their risk of experiencing adverse events such as stroke and reoperation.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
TARGETING ROS-INDUCED DAMAGE RESCUES THE DIABETIC HEART
Funder
National Health and Medical Research Council
Funding Amount
$487,669.00
Summary
Over 1 million Australians have diabetes. Many of these patients die from cardiovascular disease. We have identified free radicals as a major cause of decreased pumping function and impaired recovery from each heartbeat in the diabetic heart. Stronger antioxidant approaches and-or activation of protective protein pathways is a more effective treatment for reversing impaired function in the diabetic heart, preventing or delaying heart failure in patients with diabetes.
Structural And Drug Discovery Studies Of Oxidative Stress Regulator, Thioredoxin-interacting Protein
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, ....Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, has been recently discovered. The amount of TXNIP is increased in such conditions as high glucose, a first sign of diabetes, and under ischemia, a shortage of blood supply occurring during heart attack. This weakens the anti-oxidant defense systems and makes the organism more vulnerable to ROS exposure. Our team of researchers embarked on structural and functional studies of TXNIP with the purpose to identify small molecules that can interfere with the undesirable action of TXNIP. These molecules might become useful therapeutic agents to counteract weakening organism's ROS defense system caused by TXNIP in many disease conditions such as, cancer, diabetes and cardiac failure.Read moreRead less
Reversing Oxidative Inhibition Of The Na-K Pump By Beta3 Adrenergic Agonists: Implications For Heart Failure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Heart failure is a debilitating condition characterised by a decreased heart pump function. Raised Na+ levels and increased oxidative stress in cardiac cells are important in its causation. While traditional antioxidants are not useful in treatment, we have found that a group of drugs designed to induce weight loss can reverse oxidative inhibition of the mechanism that pumps Na+ out of heart cells. The effect of these drugs on the Na+ pumping mechanism and heart failure will be examined.
Substrate Mapping And Ablation Of Ventricular Tachycardia
Funder
National Health and Medical Research Council
Funding Amount
$444,129.00
Summary
Sudden death is a tragic occurrence and can afflict Australians of all ages, racial and ethnic backgrounds. This research will aim to understand abnormalities in the heart muscle that cause dangerous heart rhythm abnormalities, which is the most common cause of sudden death. We will study ways to improve the technology of keyhole cardiac procedures so that it can be used to prevent these arrhythmias from occurring in the first place, and in improving the chance of long-term successful cure.
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less