Manipulation Of Intracellular Arginine Content In Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$476,264.00
Summary
The lining layer of blood vessels (termed the 'endothelium') plays a vital role in the control of blood vessel function. Recently it has been shown that risk factors for heart and vascular disease (smoking, high blood pressure, high cholesterol and diabetes), heart attack and heart failure are associated with an abnormally functioning endothelium. In particular, the endothelium maintains blood vessels in a relaxed state, prevents the formation of blood clots (which may cause heart attack and str ....The lining layer of blood vessels (termed the 'endothelium') plays a vital role in the control of blood vessel function. Recently it has been shown that risk factors for heart and vascular disease (smoking, high blood pressure, high cholesterol and diabetes), heart attack and heart failure are associated with an abnormally functioning endothelium. In particular, the endothelium maintains blood vessels in a relaxed state, prevents the formation of blood clots (which may cause heart attack and stroke) and prevents the thickening of blood vessels. These important actions of the endothelium are explained by the production of nitric oxide (NO) a small chemical messenger that is derived from an amino acid, L-arginine, which circulates in blood. The amount of NO produced by endothelial cells is very dependent on the amount of arginine available, and this is determined by a careful balance between the amount of arginine taken (transported) into cells and the amount that is destroyed (metabolized) by an enzyme called arginase. Research undertaken in our laboratory is directed at understanding the important balance between arginine transport and arginase activity, as a basis for identifying new ways to prevent and treat cardiovascular disease. The current proposal describes a series of studies which will critically examine the importance of arginine transport and arginase activity, using transgenic models of over-activity and under-activity of these systems. Once established we will test the possibility that manipulating these systems may prevent atherosclerosis.Read moreRead less
A Randomised Controlled Trial Of L-arginine And-or Vitamin D To Improve Outcomes In Pulmonary Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$942,297.00
Summary
Two nutrients, arginine and vitamin D, are used by defence cells in our lungs to kill the tuberculosis bacteria. We will test whether giving arginine and-or vitamin D to people with TB (in addition to their usual TB medications) will help them recover faster and cause less long-term lung damage. We will also check whether these nutrients make them less infectious to other people.
Endothelial Dysfunction As A Therapeutic Target In Severe Malaria
Funder
National Health and Medical Research Council
Funding Amount
$842,329.00
Summary
Even with very best drugs to kill malaria parasites, over 15% of patients with severe malaria still die. Their blood vessels are clogged up by malaria parasites. We have shown that the cells lining their blood vessels can't make enough nitric oxide to keep them non-sticky and allow blood through. We want to test whether giving arginine can 1) increase nitric oxide, 2) open up the clogged blood vessels and 3) dampen down other processes that clog up blood vessels in severe malaria.