The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for matching energy supply to energy demand by the many different cells in our bodies. AMPK is active in the heart, where it may control cardiac function and the response of the heart to disease. It has been difficult to study AMPK in the heart because we lack drugs that block the actions of AMPK. This study will investigate the role of AMPK in the heart using a genetic approach whereby the AMPK enzyme is re ....The AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for matching energy supply to energy demand by the many different cells in our bodies. AMPK is active in the heart, where it may control cardiac function and the response of the heart to disease. It has been difficult to study AMPK in the heart because we lack drugs that block the actions of AMPK. This study will investigate the role of AMPK in the heart using a genetic approach whereby the AMPK enzyme is rendered inactive (a gene knockout approach). By this approach we will learn how AMPK controls heart function and how drugs that affect AMPK may impact on the heart.Read moreRead less
Invasive Assessment Of Pulmonary Vascular Physiology - Novel Methods For Early Detection Of Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$274,352.00
Summary
Pulmonary vascular disease (PVD) is a lethal condition characterised by progressive destruction of the lung blood vessels. One major problem with PVD is that diagnosis is often made very late in the illness, when the pulmonary blood pressure rises. This project aims to develop a novel method to detect the early and clinically silent phase of PVD, by assessing the lung's blood vessel reserves. Early diagnosis of PVD will enable earlier treatment thereby improving prospects for treatment.
Mechanisms Responsible For Hypertension Caused By Perinatal Omega-3 Fatty Acid Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$280,650.00
Summary
Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) ....Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) for the first time that the essential omega-3 fatty acid, alpha-linolenic acid (ALA), supplied in the early developmental period, affects blood pressure later in life. The work showed that moderate omega-3 fatty acid deficiency in the perinatal period resulted in hypertension, despite reversal of the deficiency at a time months before the assessment of blood pressure. These findings are suggestive of a critical period, during which time the development of normal blood pressure control mechanisms appears, at least partially, dependent upon the supply of omega-3 fatty acids. These findings suggest that omega-3 deficiency early in life may affect fatty acid metabolism, transport or uptake systems, such that re-feeding of the nutrients is functionally ineffective. Alternatively, deficiency of omega-3 fatty acids early in life may arrest development of one or more of the key signalling pathways in the control of blood pressure, such as the Brain Angiotensin System. The influence of dietary omega-3 fatty acid supply, relative to the critical period, on expression of genes involved in the control of blood pressure as well as in fatty acid metabolism, will be defined. Also, the role of the brain angiotensin system in omega-3 fatty acid deficiency-induced hypertension will be determined. We expect that the results of this study will profoundly affect hypertension research, as well as nutrition, particularly that for infants.Read moreRead less
Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
Effects Of Ghrelin Receptor Ligands On Cardiovascular Function
Funder
National Health and Medical Research Council
Funding Amount
$516,207.00
Summary
Ghrelin is a hormone that is known to control food intake and growth hormone release. Our recent work shows that compounds that mimic ghrelin�s actions influence blood pressure by their effects in the brain, the spinal cord and on arteries. We will investigate the potential of such compounds to treat blood pressure disorders
Heart-lung Interactions Determine Right Ventricular Function In The Perinatal Period.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, ....Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, as many as 5,000 require intensive care primarily for cardiorespiratory complications. Accurate diagnosis and effective treatment of these infants demands knowledge of the normal heart adaptations that accompany birth, adaptations that are critically linked to the way in which the heart and the lungs interact. This project investigates how interactions between the heart and the lungs determines heart function throughout life. By understanding this process we will provide essential information that will aid the diagnosis and treatment of sick neonates undergoing intensive care.Read moreRead less
The Effects Of Maternal Glucocorticoid Administration In Growth Restricted Fetuses.
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are th ....Antenatal administration of glucocorticoids to pregnant women at risk of preterm delivery has been shown to enhance fetal lung maturation. However, glucocorticoids such as betamethasone have a range of potentially deleterious non-pulmonary effects, which include significant alterations in fetal cardiovascular function. This is important because intrauterine growth restricted (IUGR) fetuses constitute a significant proportion of pregnancies in Australia, are at risk of preterm delivery and are therefore likely to receive maternal betamethasone. From both human observations and animal studies, it is well documented that IUGR fetuses demonstrate a range of cardiovascular adaptations that ensure maintenance of oxygen delivery to vital organs despite reduced placental perfusion. However, in recent clinical and experimental studies we have demonstrated that administration of betamethasone to IUGR fetuses induces changes in fetal blood flow that may be detrimental to the IUGR fetus. Specifically, we believe that glucocorticoids may increase the risk of both cardivascular and cerebral damage in the growth restricted fetus. The significance of these findings and the mechanisms regulating these changes remain unclear but they have clear implications for future clinical management. This proposal represents the further development of preliminary experimental studies to examine the effects of betamethasone in the ovine IUGR fetus with future clinical care in mind.Read moreRead less
Investigation Of The Influence Preterm Birth On Lung Structure And Function In School Age Children.
Funder
National Health and Medical Research Council
Funding Amount
$204,482.00
Summary
Bronchopulmonary dysplasia (BPD) remains the most significant chronic lung complication of premature birth. While some information on the long term respiratory outcomes in BPD exist there are no comprehensive studies linking lung structure, function and respiratory symptoms and relating these changes to neonatal history. Studies of this kind are essential to ensure future healthcare for these children can be planned accordingly.
The Role Of The Cytoskeleton In Communication Between The L-type Ca2+ Channel And The Mitochondria In Cardiac Pathology
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
The L-type calcium channel is a protein in the membrane of heart muscle cells responsible for maintaining normal rhythm and contraction. We have shown that the channel can also regulate the function of the energy producing part of the cell (mitochondria). This occurs with the assistance of proteins that maintain cell architecture. We will test whether this association is altered in human disease where the cell architecture is disrupted to determine the mechanisms for poor energy supply.
There is increasing evidence that regular physical activity contributes considerably to better physical fitness and good health of individuals and nations. Unfortunately, many individuals in Australia are not regularly active. A sedentary lifestyle is associated with a higher risk of coronary heart disease, obesity, diabetes, osteoporosis and some cancers. Physical activity guidelines encourage participation in at least 30 minutes of moderate-intensity physical activity on most, preferably all, ....There is increasing evidence that regular physical activity contributes considerably to better physical fitness and good health of individuals and nations. Unfortunately, many individuals in Australia are not regularly active. A sedentary lifestyle is associated with a higher risk of coronary heart disease, obesity, diabetes, osteoporosis and some cancers. Physical activity guidelines encourage participation in at least 30 minutes of moderate-intensity physical activity on most, preferably all, days of the week. Walking is one of the most common forms of physical activity undertaken by adults, however there is a relatively poor understanding of the physiological demands of this task. A better understanding of walking for people of different age, gender, size and shape would provide for improvements in the categorisation of intensity of physical activity for use in population measures of physical activity and exercise prescription for individuals who are obese. The aim of the proposed study is to assess the relationship between energy cost of walking and body composition of adults. The main purpose is to consider how people of different age, gender, size and shape manage self-paced walking relative to maximal capacity. The energy cost of walking is an important determinant of a person's functional capacity, physical fitness and health status. The main outcomes of the study: An increased knowledge and understanding of the energy expenditure of self-paced walking relative to maximal aerobic power; More reliable assessment of physical activity status using a variety of commonly employed indirect assessment techniques; A comprehensive understanding of the inter-individual differences in walking characteristics based on age, gender or body fatness; A better understanding of the energy cost of walking and the subsequent promotion of this form of physical activity has potential to impact on the health of Australians, particularly those who are sedentary and overweight or obese.Read moreRead less