Characterisation Of MiRNAs That Regulate Vascular Leakage.
Funder
National Health and Medical Research Council
Funding Amount
$167,493.00
Summary
Vascular permeability or leak is a major problem in diseases such as cancer and in cardiovascular diseases . MicroRNAs (miRNAs) are small control genes that influence dveleopment and disease. We have identified a miRNA cluster in endothelial cells, the cells that line the blood vessels, that is important in the control of vascular leak. This project is focused on understanding the impact of these miRNAs in disease.
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less
Vascular Targeting Combined With Radiosurgery In An Arteriovenous Malformation Rat Model
Funder
National Health and Medical Research Council
Funding Amount
$102,345.00
Summary
Cerebral arteriovenous malformations are an important cause of stroke and brain bleeds. In many patients such a stroke can result in severe disability or death. Current management involves a combination of surgery, radiation therapy and endovascular treatments and carry a high risk of complications. This research project suggests a new form of treatment whereby irradiating the vascular malformation a medication could be administered to cause targeted clotting of the malformation.
Growth Regulatory Transcriptional Networks And Novel Therapies In Vascular Pathobiology
Funder
National Health and Medical Research Council
Funding Amount
$576,760.00
Summary
Cardiovascular disease and cancer together account for the majority of all deaths. Underpinning both these conditions are cellular and molecular changes in our blood vessels. This Fellowship will enable Professor Khachigian to enhance our understanding of fundamental mechanisms regulating the pathogenesis of vascular disease, and by harnessing this new knowledge in preclinical and human trials, generate novel strategies to combat a range of diseases through strategic partnership, collaboration a ....Cardiovascular disease and cancer together account for the majority of all deaths. Underpinning both these conditions are cellular and molecular changes in our blood vessels. This Fellowship will enable Professor Khachigian to enhance our understanding of fundamental mechanisms regulating the pathogenesis of vascular disease, and by harnessing this new knowledge in preclinical and human trials, generate novel strategies to combat a range of diseases through strategic partnership, collaboration and training.Read moreRead less
A Study Of The Origins Of Macrophages In Healthy And Atherosclerotic Vasculature Focusing On A Novel Population Of Resident Adventitial Macrophage Progenitor Cells (AMPCs)
Funder
National Health and Medical Research Council
Funding Amount
$465,345.00
Summary
White blood cells (macrophages) play a key role in the development of atherosclerosis, the underlying cause of most heart attacks and strokes. We have made new discoveries to show that there are stem (progenitor) cells for macrophages that exist within the outer lining of blood vessels. This project will study whether these local progenitor cells, called AMPCs, are a source of macrophages in atherosclerosis and in turn could lead to new treatment approaches for cardiovascular disease.
How Does Activated Protein C Create Intact, Non-leaky, Stable Blood Vessels?
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Vascular dysfunction is a common feature of many diseases, including sepsis, diabetes, atherosclerosis, tumours and asthma. These vessels have compromised structural and functional integrity, leading to leakage of blood components and causing inflammation in tissues. Based on our recent findings, this project aims to discover how activated protein C creates normal, healthy non-leaky blood vessels and prevents vascular dysfunction in disease.
Targeting Renal And Vascular Inflammation In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$781,589.00
Summary
Inflammation is a hallmark of high blood pressure (A.K.A. hypertension) and underlies clinical complications of the condition such as kidney failure and blood vessel disease. This project will investigate whether a recently described signaling complex termed the 'inflammasome' is a trigger of inflammation in hypertension in the hope of identifying it as a target for new drugs that are more effective in the treatment of hypertension and its complications.
The Role Of Tissue Factor Pathway Inhibitor (TFPI) In The Pathogenesis Of Lymphatic Malformations
Funder
National Health and Medical Research Council
Funding Amount
$87,198.00
Summary
Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condit ....Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condition.Read moreRead less