Atrial Electrical Remodeling Due To Chronic Stretch: Defining The Substrate For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood ....Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood. There are several forms but the basic problem is leakage of blood from the left atrium into the right atrium .This also puts a strain on the heart and can cause heart failure. All 3 conditions are associated with a significantly increased risk of atrial fibrillation (AF). This abnormal fast irregular cardiac rhythm makes the pumping of the heart inefficient. People with AF may feel short of breath, tired, or develop palpitations. AF is an important cause of stroke and premature death and is the most common heart rhythm disturbance occurring in upto 10% of the over 70 age group. Even after repair of the leaky valve or atrial septal defect there is still a high risk of developing this rhythm. Purpose of the study: This study will try to understand why patients with these conditions are at risk of developing atrial fibrillation, and why this risk might persist after surgical correction when this is possible (mitral regurgitation and atrial septal defect). The study will utilise sophisticated new mapping techniques to gain original insights into the mechanism of this very common and as yet poorly understood heart rhythm disturbance. The study has the potential to determine the cause of atrial fibrillation in these patient groups and as such represent a quantum advance in our understanding of he mechanism of atrial fibrillation. It would be expected to form a foundation on which development of curative and preventative approaches may be based.Read moreRead less
Clinical, Pathological And Genetic Basis Of Familial Valvular Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Mitral valve prolapse and bicuspid aortic valve are two common valve syndromes that are characterized by remarkable clinical diversity, ranging from no symptoms to potentially life threatening complications, heart failure and sudden death. Both disorders seem to run in families in a significant proportion of patients and thus are likely to have genetic causes, which remains unknown to date. This project aims to identify the underlying genetic basis of these common familial valve syndromes.
A Transgenic Analysis Of The Physiologic Roles Of Signalling Domains In The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$262,500.00
Summary
The key hormone promoting growth postnatally is growth hormone (GH), and it acts through the growth hormone receptor to initiate a variety of signals which regulate gene expression. In addition to its role in growth, GH is an importnat metabolic regulator in starvation. It also appears to play a significant role in the ageing process, since mice lacking the GH receptor live 50% longer than normal mice. Although the signalling systems used by the GH receptor are reasonably well defined in vitro, ....The key hormone promoting growth postnatally is growth hormone (GH), and it acts through the growth hormone receptor to initiate a variety of signals which regulate gene expression. In addition to its role in growth, GH is an importnat metabolic regulator in starvation. It also appears to play a significant role in the ageing process, since mice lacking the GH receptor live 50% longer than normal mice. Although the signalling systems used by the GH receptor are reasonably well defined in vitro, we have no idea which signals are used to control postnatal growth, metabolism and ageing in the live animal. With NHMRC support, we have been creating mice with individual signalling domains of the GH receptor deleted. This proposal aims to use these mice to determine how the GH receptor brings about its actions of promoting postnatal growth, regulating metabolism and altering lifespan. In particular, through the use of gene arrays, we intend to define the key genes regulated in these processes. This would provide potential therapeutic targets for drug development to individually alter these key processes.Read moreRead less
Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, ....Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.Read moreRead less
Developing A Screening Test To Identify Women At Risk Of Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$1,119,284.00
Summary
Preeclampsia is a serious complication of pregnancy for which there is currently no cure and no way to accurately predict women at risk. Using large collections of human blood samples, we will screen for novel proteins within pregnant women's blood. We will then use artificial intelligence to select the best biomarkers and combine them with clinical information to develop a multi-marker blood test to predict women at risk.
Decidual-trophoblast Interactions Critical For Optimal Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$612,927.00
Summary
This proposal seeks to identify the critical maternal and embryonic placental factors that regulate the formation of a healthy placenta and thus a healthy pregnancy and baby. Currently there is no way of identifying whether the placenta is forming adequately. The proposed studies are a necessary first step in identifying therapeutic targets for diseases associated with a poorly formed placenta, such as preeclampsia.
Mechanistic And Translational Studies In Female Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The womb is essential for a health pregnancy. This research aims to determine how the womb interacts with embryos to ensure a healthy pregnancy forms. Cells in the womb can also grow abnormally and result in endometrial cancer. New treatments for endometrial cancer will also be tested in this research.
The Pathogenic Role Of A Placenta-specific Protease In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Preeclampsia (PE) is a life-threatening disorder of pregnancy. If left untreated, PE will lead to maternal as well as fetal death. Unfortunately, the only current effective “cure” for PE is to deliver the baby prematurely. The causes of PE are intrinsically related to the placenta, the organ that connects the fetus to the mother. This project will investigate a unique enzyme that is produced only by the placenta, its contribution to PE and its potential as a target for PE treatment.
Blood Pressure Effects On Placental Growth And Development
Funder
National Health and Medical Research Council
Funding Amount
$133,357.00
Summary
Diseases causing high blood pressure in pregnancy or preeclampsia are a major cause of complications in mother and infant. At present, the only treatment is delivery of the baby who may be premature or too small. Why preeclampsia develops is incompletely understood and the long term consequences of this disease for the mother includes doubling of the future risk of heart and kidney disease. This research will look at the placenta or afterbirth at a molecular level to better understand why this d ....Diseases causing high blood pressure in pregnancy or preeclampsia are a major cause of complications in mother and infant. At present, the only treatment is delivery of the baby who may be premature or too small. Why preeclampsia develops is incompletely understood and the long term consequences of this disease for the mother includes doubling of the future risk of heart and kidney disease. This research will look at the placenta or afterbirth at a molecular level to better understand why this disease occurs.Read moreRead less