Heart muscle cells have little potential for regeneration, and after a heart attack or in response to chronic hypertension, they grow bigger, resulting in deterioration of function and heart failure. We have compelling evidence that the c-kit protein limits heart regeneration and function. We expect to demonstrate that c-kit inactivation can greatly improve heart regeneration and function after cardiac injury/stress. Our work will have major clinical significance for future heart failure treatme ....Heart muscle cells have little potential for regeneration, and after a heart attack or in response to chronic hypertension, they grow bigger, resulting in deterioration of function and heart failure. We have compelling evidence that the c-kit protein limits heart regeneration and function. We expect to demonstrate that c-kit inactivation can greatly improve heart regeneration and function after cardiac injury/stress. Our work will have major clinical significance for future heart failure treatment strategies.Read moreRead less
Is Sympathetic Activation Beneficial Or Detrimental In Septic Shock?
Funder
National Health and Medical Research Council
Funding Amount
$458,755.00
Summary
Septic shock is a major cause of death in intensive care units. It is associated with large increases in sympathetic nerve activity to the heart and kidneys, which have both beneficial and harmful effects. This project will determine the responses to the increased sympathetic activity in septic shock, the causes of it and whether blocking this activation has an overall beneficial effect. This knowledge is essential before drugs that block sympathetic activation are examined in clinical studies.
Understanding The Opposing Roles Of SWI-SNF In The Control Of Gene Programs For Pathological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$476,258.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
NOVEL CGMP-BASED THERAPIES PREVENT LEFT VENTRICULAR REMODELLING
Funder
National Health and Medical Research Council
Funding Amount
$533,433.00
Summary
Over 300,000 Australians are affected by heart failure. Current drugs for cardiac remodelling (the decline in heart pumping function and changed structure that precede heart failure) slow but not reverse disease progression. We have identified a new, nitrovasodilator-based therapy superior to those currently available. We propose it represents a more effective treatment for reversing abnormalities in both structure and function in the remodelled heart, preventing or delaying heart failure.
Gastric, Small Intestinal And Cardiovascular Mechanisms Of Postprandial Hypotension.
Funder
National Health and Medical Research Council
Funding Amount
$701,521.00
Summary
A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, and is associated with an increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for postprandial hypotension are not well understood and current therapies are less than optimal. The studies proposed in the current application have important implications for the management of postprandial hypotension.
Unique Isoform-specific Regulation Of Cardiac Ryanodine Receptors By Calcium Store Proteins
Funder
National Health and Medical Research Council
Funding Amount
$421,160.00
Summary
The importance of proteins that regulate calcium stores of heart muscle is graphically illustrated by massive changes in cell structure and function, which lead to ventricular fibrillation and fatality when the proteins are disrupted. We recently made the remarkable discovery that the proteins have a unique action in the heart which enhances cardiac contraction. We will discover the interaction sites between the proteins and will define novel therapeutic targets for heart failure.