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.
Novel Treatments Of Fibrosis For Hypertensive Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$912,536.00
Summary
A recognised risk factor for cardiovascular disease is high blood pressure which contributes to a stiffer heart that can ultimately lead to heart failure. There are very few treatments that can reduce heart stiffening, called fibrosis. This project is focused on the preclinical testing of novel compounds that we have developed to reverse the build-up of fibrosis in the heart, which will lead to better treatment of elderly patients with high blood pressure and poorly-functioning hearts.
The Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse 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.
Modulating Pathogenic Signalling Towards The Prevention Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Diabetes is associated with an increased risk of heart attacks and kidney failure. There remains an urgent need for new targets and therapies for preventing, arresting, treating and reversing these diabetic complications. My research directly focuses on identifying and validating these targets treatments, building on strong preliminary data and understanding of the molecular mechanisms set off by high sugar levels.
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.
ACE2, A New Regulator Of The Renin Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$492,625.00
Summary
Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, AC ....Angiotensin converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS), converting Angiotensin I to the potent vasoconstrictor Angiotensin II (Ang II). ACE inhibitors have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and also reduce the rate of progression of renal disease. Recently, a novel enzyme called ACE2 has been discovered in the heart and kidneys. Unlike ACE, ACE2 causes the formation of the vasodilator, Ang 1-7. We have data in the heart and the kidney that supports the concept that ACE2 acts in a counter-regulatory manner to ACE. We suggest that ACE2 may play an important role to modulate the balance between vasoconstrictors and vasodilators in the heart and kidney. The studies detailed in this proposal are designed to specifically examine the role and regulation of ACE2 in the healthy heart and kidney as well as in cardiovascular and renal disease. The project brings together two groups with complementary skills and techniques, both of whom have collaborations with the discoverers of ACE2, and who have been exploring the role of ACE2 as evidenced from our recent publication (Tikellis et al, Hypertension in press, 2003).Read moreRead less