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
A Novel Approach To Streamlining The Diagnosis Of Primary Aldosteronism
Funder
National Health and Medical Research Council
Funding Amount
$269,463.00
Summary
This study will assess a new clinical test used to diagnose a potentially curable form of high blood pressure called primary aldosteronism (PA). If successful, the test will greatly streamline and simplify the diagnosis of this condition, with the potential for enormous cost savings and a markedly increased rate of diagnosis of patients with PA who can then benefit from optimal treatment and improved quality of life.
Determinants Of Tissue- And Ligand-Specific Responses At The Mineralocorticoid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$668,485.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.
Targeting Aldosterone Receptors In Cerebrovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,712.00
Summary
Stroke represents a major health (accounting for 6% of all deaths) and economic (costs Australia $2.14 billion per year) burden on society, thus clearly more effective treatments are needed. This project will investigate the role of two substances produced in the body – angiotensin II and aldosterone – in stroke outcome, and whether targeting their receptor(s) may prevent poor outcomes following stroke.
Cardiovascular disease is a leading cause of death in Australia, accounting for 36% of all deaths in 2004-05. Diseased blood vessels are its most common form, and the underlying process is atherosclerosis. Atherosclerosis is characterised by plaque formation in blood vessels. Plaque formation is problematic, and may lead to blood vessel blockage. We aim to identify novel targets that prevent plaque formation.
Mineralocorticoid Receptors - Mechanisms Of Ligand- And Tissue- Specific Activation
Funder
National Health and Medical Research Council
Funding Amount
$126,848.00
Summary
Heart disease is a major cause of death and economic burden in Australia and throughout the world. The steroid hormone aldosterone controls salt and water balance, blood pressure and has a significant role in heart failure. Although drugs that block the aldosterone receptor significantly help patients with heart failure, their use is limited by side effects. This work will identify the profile of proteins that promote aldosterone effects and enable the development of heart-specific blockers.