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.
Diabetic Cardiomyopathy: Defining New Mechanisms Of Cardiomyocyte Injury And Loss
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The heart is recognized as an important casualty organ in the progression of diabetes – both type 1 and type 2. We have new evidence that in diabetic and pre-diabetic hearts there is excess breakdown of heart cell structure in order to scavenge metabolic fuel, and that this scavenging can lead to heart cell death. Our goal is to identify ways in which the heart may be protected against this pathology and to identify new molecular targets for treatment of diabetic hearts.
Cardiac Dysfunction In Diabetes: A Novel Therapeutic Approach
Funder
National Health and Medical Research Council
Summary
Diabetes is a global epidemic with high mortality associated with heart failure. I propose a new hypothesis: diabetic heart failure reflects a progressive decline in heart pump efficiency due to an accumulation of large glycogen stores in heart muscle cells. This research aims to characterise the underlying causes of heart failure in diabetes and identify intervention potential to rescue function and prevent the progression into failure.
ANNEXIN-A1 MIMETICS: A NOVEL THERAPEUTIC APPROACH FOR TARGETING THE CARDIAC COMPLICATIONS OF DIABETES
Funder
National Health and Medical Research Council
Funding Amount
$815,185.00
Summary
Diabetes affects almost 2 million Australians, creating an increasing heart failure burden. A/Prof Rebecca Ritchie’s team at Baker IDI are interested in the precise role of cardiac inflammation in the progression of cardiomyopathy resulting from diabetes. Using her exciting discovery that a naturally-occurring anti-inflammatory protein is a key regulator of cardiac muscle cell survival and function, A/Prof Ritchie’s team will develop therapies for diabetic cardiomyopathy based on this protein.
Research Fellowship: Protection Of Myocardial Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Heart failure (HF) is a major cause of death in Australia. A/Prof Rebecca Ritchie heads Heart Failure Pharmacology at Baker IDI. Her research focuses on new drug strategies to maintain heart function in response to diabetes & heart attack, common precursors of HF. Many of the treatments discovered from this work are naturally-occurring antioxidants; enhancing their activity will ultimately reduce progression to HF & death in the >3 million Australians affected by these disorders.
Pre-clinical Development Of A Novel Anti-fibrotic, Anti-inflammatory Compound To Treat Diabetic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$488,391.00
Summary
Diabetic patients are prone to developing chronic heart failure. In the diabetic heart, scar tissue accumulates within the muscle (fibrosis), impairing function. We have developed a new drug to treat fibrosis in diabetic kidney disease (FT-11), and have approval for pre-clinical development of this drug. We now aim to test whether FT-11 is also effective in reducing fibrosis in the diabetic heart, and whether this can prevent heart failure in an animal model of diabetic heart disease.
Role And Mechanism Of Connective Tissue Growth Factor In Diabetic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$382,820.00
Summary
Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen pa ....Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen patient outcomes. We have generated data in experimental diabetes in rodents that strongly implicates a heart growth factor in causing diabetic cardiomyopathy. This protein, called connective tissue growth factor (CTGF), is increased in diabetic cardiomyopathy, and is elevated by high glucose and other factors in diabetes. We have published data showing that CTGF causes tissue scarring like that which occurs in cardiomyopathy, by affecting signals in cells called fibroblasts. It increases the laying down of extracellular matrix (ECM) and also inhibits the degradation of ECM by the proteins that break down matrix, known as the MMPand PAI systems. Such accumulation of ECM is thought to be a major factor leading to abnormal muscle function in cardiomyopathy. We now plan to block CTGF in this diabetic heart model to determine if we can prevent diabetic cardiomyopathy. We have generated two methods to inhibit CTGF in the animal model. Echocardiography (a heart ultrasound test), and molecular analysis of the heart tissue will determine if we can prevent the otherwise adverse functional and structural changes of diabetes in the heart. We will also study our baboon model of diabetes to determine if diabetic cardiomyopathy with increased heart CTGF is present in the primates. Cell culture studies from rat heart fibroblasts and myocytes will determine how CTGF has the effect on cells to cause cardiomyopathy and how we might further prevent this condition developing in diabetes.Read moreRead less
My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.
Characterisation Of Novel AGE Binding Proteins: Implications For Diabetic Vascular Complications.
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This i ....This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.Read moreRead less