Obesity And AF: Characterisation And Reversibility Of The Clinical Substrate
Funder
National Health and Medical Research Council
Funding Amount
$337,180.00
Summary
Over the last 5 years, I have characterized the atrial fibrillation (AF) substrate in obese sheep model. My goal is now to translate this work to the clinic and confirm the mechanisms of AF in obese patients and their reversibility with weight reduction with a specific aim to identify targets for intervention. Over this period, I intend to establish myself as an independent researcher with the long-term goal of developing effective prevention and management strategies for AF in obesity.
Understanding The Cardio-protective Actions Of The AT2R In Females: Shifting Gears Between AT1 And AT2 Receptor Balance Of Function With Relaxin.
Funder
National Health and Medical Research Council
Funding Amount
$1,049,288.00
Summary
Women are protected from cardiovascular disease as compared to age-matched men, an effect lost with age. Understanding protective factors that act in females could be used to treat hypertension, heart failure and stroke in males at all ages, and maintain protection in elderly women. Our studies aim to determine if relaxin, an ovarian hormone, can promote cardiovascular health in women.
Regulation Of Mammalian Heart Regeneration By The MiR-15 Family.
Funder
National Health and Medical Research Council
Funding Amount
$435,859.00
Summary
The inability of the adult heart to regenerate following a heart attack is a major contributor to the burden of heart disease in the developed world. We have recently discovered that, for a brief period after birth, the newborn heart can completely regenerate itself following injury. Understanding how and why the heart loses this remarkable capacity for regeneration shortly after birth may hold the key for developing cardiac regenerative therapies.
Role Of Myeloperoxidase In Endothelial Barrier Dysfunction During Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The release of the enzyme myeloperoxidase (MPO) within blood vessels is thought to affect their ‘leakiness’ during periods of inflammation, leading to fluid associated swelling (oedema). We propose that MPO produces oxidant chemicals that increase blood vessel leakage. The aim of our work is to study how these chemicals increase vascular leakage by studying the biochemical pathways involved. These studies could lead to new intervention strategies targeting MPO to reduce excessive tissue oedema.
Cellular Localisation Of Mineralocorticoid Receptor-mediated Vascular Inflammation And Cardiac Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$476,264.00
Summary
Cardiovascular disease is a major health and economic burden throughout the world, especially in developed countries and is the leading cause of death and disability in Australia, claiming the lives of over 50,000 Australians each year. Heart failure accounts for many of these deaths and the incidence continues to increase. Two recent large scale clinical trials have shown a 30-35% improvement in patient outcome when a blocker for the mineralocorticoid receptor (MR) is included in current best p ....Cardiovascular disease is a major health and economic burden throughout the world, especially in developed countries and is the leading cause of death and disability in Australia, claiming the lives of over 50,000 Australians each year. Heart failure accounts for many of these deaths and the incidence continues to increase. Two recent large scale clinical trials have shown a 30-35% improvement in patient outcome when a blocker for the mineralocorticoid receptor (MR) is included in current best practice therapy for either heart failure or after a heart attack. The mechanisms underlying these benefits remain to be identified. We have shown that the hormone aldosterone and its receptor, the MR, not only play an important role in the development of high blood pressure but also the progression of cardiac disease. Our most recent studies have shown that blocking the MR not only prevents cardiac fibrosis and vascular damage, but also reverses this process. To understand the mechanisms that translate MR signalling into blood vessel damage and cardiac fibrosis we wish to use mice who have the MR gene inactivated in specific cells only. In this way we can identify those cells critical to the disease process and focus our investigations to these cell types. Understanding the cell specific regulatory mechanisms for the MR may enable the development of heart-specfic blockers of the MR that have minimal, if any side effects.Read moreRead less