Influence Of Endothelin And Protease-activated Receptors On Eosinophil Trafficking In The Airways Of Allergic Mice
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of as ....Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of asthma sufferers also become inflamed and the resulting swelling of the airways and excess formation of mucous makes breathing difficult. Inflamed asthmatic airways contain large numbers of cells called eosinophils, which move from the blood into the airways. Substances released from the eosinophils are thought to damage the airways and cause airways hyperresponsiveness. We have developed a mouse model of allergic inflammation which has many of the hallmark features of asthma, including high numbers of eosinophils and hyperresponsive airways. We have recently shown that these effects are inhibited by treatment of allergic mice with a drug called SB217242. SB217242 inhibits the actions of endothelin, a peptide that is produced in elevated amounts in the airways of asthma sufferers and which may produce many of the effects associated with asthma. We wish to investigate the mechanisms through which SB217242 and drugs which stimulate novel protease-activated receptors inhibits the increase in eosinophil numbers in the airways. We will investigate the possibility that these drugs inhibit the migration of eosinophils from the blood into the airways, using a unique microscope that allows us to visualize the movement of eosinophils into tissues such as the airways. These studies are likely to be of considerable strategic value in determining the potential usefulness of these drugs in the treatment of asthma.Read moreRead less
Double Blind, Randomised Controlled Trial Assessing The Efficacy Of Endothelin-1 Receptor Antagonism In Preventing Peri-procedural Myonecrosis In Patients With Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Funder
National Health and Medical Research Council
Funding Amount
$124,608.00
Summary
While the focus in the treatment of coronary artery disease has primarily been on the large vessels in the heart, vessels of small calibre may also play a significant role in patients with angina, heart attack, and muscle injury related to a stenting procedure.This project aims elucidate the possible mechanisms which cause dysfunction in these small vessels. I also hope to find a treatment strategy which may benefit patients with small vessel problems and thus improve their overall outcome.
Regulation Of Endothelin Converting Enzyme Subcellular Distribution And Vascular Endothelin Production.
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not ....Endothelin is a hormone produced by the endothelial cells that line blood vessels. The role of this hormone is cause blood vessels to constrict (vasoconstriction), thus causing a rise in blood pressure. The synthesis of this hormone is crucially dependant on an enzyme that has to be located on the surface of the endothelial cell. The aim of this grant is to understqand the mechanisdms by which the location of this enzyme within the cell is regulated. The knowledge gained from this study will not only help us better understand the mechanism of endothelin production but it may also offer an insight into future therapeutic startegies to prevent the formation of endothelin, thus preventing vasoconstriction.Read moreRead less