Regulation Of The Placental Renin-angiotensin System By MicroRNAs; Implications For Pregnancies Complicated By Placental Insufficiency?
Funder
National Health and Medical Research Council
Funding Amount
$483,058.00
Summary
Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their ea ....Intrauterine growth restriction (IUGR) and preeclampsia (PrE) are life threatening to mother and baby, making the baby susceptible to disease as an adult. One of the major causes of PreE and IUGR is placentation. Placentation is affected by the placental renin-angiotensin system (RAS), which is controlled by microRNAs. We will describe these microRNAs, what controls them; determine their expression and RAS expression in normal pregnancy, IUGR and PrE, thus providing novel biomarkers for their early detection.Read moreRead less
Mechanisms Involved In Reduced Cardiac Contractility As A Consequence Of Growth Restriction During Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$317,810.00
Summary
Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal phy ....Functional development of the heart muscle has been a focus of intense research over the last 40 years. Despite our current understanding of the changes in how excitation of the cardiomyocyte leads to contraction, a process broadly termed excitation-contrcation (E-C) coupling, a major model used to study paralells of human fetal development, the sheep, has not been examined in this context. As such, it remains unclear how E-C coupling evolves from the fetus to the adult. Understanding normal physiology is imperative to subsequetly understand pathological states, such as interuterine growth restriction (IUGR). In Australia, the incidence of IUGR leading to low birth weight babies is 7%. IUGR is caused by maternal undernutrition, maternal smoking-drug use and placental insufficiency. It is associated with an increase in perinatal mortality, respiratory problems, SIDS and morbidity. Epidemiological studies show that low birth weight babies are also at an increased risk of cardiovascular disease, including heart failure, in adult life. To date, there is little information on the impact of fetal growth restriction on the normal development and function of the heart muscle. Understanding the impact of IUGR on heart muscle development will allow the elucidation of the underlying physiological mechanisms linking these two temporally distinct events. This mechanistic understanding will allow improved clinical management of those individuals at risk of cardiovascular disease in adult life arising from IUGR. It may also allow for early intervention strategies that can improve cardiovascular function. Therefore, we propose to examine both the normal developmental changes to E-C coupling so that we can understand how placental insufficiency leading to IUGR impairs normal heart muscle development. This will result in impaired function at a cellular level, which will ultimately manifest as an increased susceptibility of the heart to injury in later life.Read moreRead less
The Role Of Tissue Hypoxia In The Evolution Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,391.00
Summary
We will determine how low oxygen levels in the kidney lead to kidney disease. We can now measure the levels of oxygen in kidney tissue in rats 24 hours a day, 7 days a week, in a completely non-invasive way. We will study two common kinds of kidney disease. One, acute kidney injury, can result from administration of contrast agents used in x-ray diagnostic procedures. The other, chronic kidney disease, is common in patients with diabetes or high blood pressure.