Mechanism Of Epidermal Growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. We believe that the same cell processes are also involved in cancer cell growth and by understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease and its relationship to uncontrolled growth will evolve.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
DEFINING NONCLASSICAL ANGIOTENSIN SIGNALLING AND CARDIOVASCULAR FUNCTION
Funder
National Health and Medical Research Council
Funding Amount
$634,580.00
Summary
Angiotensin II is a hormone which is well known to contribute to high blood pressure and cardiovascular disease. This proposal will use highly novel compounds that we have synthesised that, for the first time, selectively target nonclassical angiotensin-related binding sites, so called NON-AT1 receptors, which are thought to counteract the deleterious effects of angiotensin II that normally causes fibrosis or scarring of the heart which damages healthy muscle.
Elucidation Of The Genetic Mechanisms Of Primary Aldosteronism: The Most Common, Curable Form Of Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$334,338.00
Summary
Hypertension is a major cardiovascular risk factor that affects 10-40% of the population. The steroid hormone aldosterone controls blood pressure and plays a significant role in hypertension. Primary Aldosteronism (PAL), a condition caused by the excessive production of aldosterone, is the most common, curable form of hypertension. I will identify the molecular mechanisms responsible for PAL, to advance the development of new diagnostic tools and identification of novel therapeutic targets.
Insulin Regulated Aminopeptidase: A New Cardiovascular Target
Funder
National Health and Medical Research Council
Funding Amount
$672,650.00
Summary
Cardiovascular disease, leading to heart attack or stroke is the largest cause of death in Australia. We have evidence that inhibition of a newly described enzyme (IRAP) by angiotensin IV is protective in a model of atherosclerosis. Excitingly we have preliminary data indicating that mice deficient in IRAP have better vascular function therefore we will further investigate this as well as the effectiveness of newly developed IRAP inhibitors in preventing development of cardiovascular disease.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Protective Role Of The Depressor Arm Of The Renin-angiotensin System During Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$633,384.00
Summary
The motivation for unveiling the normal hormonal and molecular mechanisms involved in the extraordinary vasodilatation associated with pregnancy is that understanding these fundamental processes may provide novel insights into the pathophysiology of preeclampsia and intrauterine growth restriction, as well as potential therapeutic strategies for not only the treatment of these pregnancy specific conditions but also cardiovascular and renal diseases in non-pregnant women and men.
Physiology Of A Mutant Angiotensin Receptor Associated With Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$293,699.00
Summary
As many as one in ten healthy individuals have hearts that are bigger than normal. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We ....As many as one in ten healthy individuals have hearts that are bigger than normal. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified a region on a rat chromosome that influences heart size and we have now discovered abnormalities in a key gene in this region. These changes alter the function of a cellular protein that mediates hormonal effects on heart cell size. Our team of experts will employ the most modern technologies to understand exactly how this altered protein affects heart cell function and growth. We have a unique opportunity to exploit this experiment of nature to help us devise new means of preventing big hearts and their fatal complications in humans.Read moreRead less