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.
Oxidative Stress, Heparan Sulfates And Endothelial Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
During vascular disease endothelial cells that line the blood lumen are dysfunctional. Growing evidence indicates a role for a protein that the immune system normally uses to destroy infectious agents. This protein accumulates in diseased blood vessels next to endothelial cells. This project will study how this protein causes endothelial dysfunction and test the ability of novel agents to remove this protein from diseased blood vessels to improve endothelial function.
Atherosclerosis: Molecular Mechanisms Of Suppression By CD4+CD25+ Regulatory T-cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Atherosclerosis, or hardening of large arteries is the underlying cause of up to 50% of deaths in Western communities, primarily from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the accumulation of fats such as cholesterol into the inner lining of blood vessels including those supply vital organs such as the heart and brain. This study focuses on understanding how to use the body's own anti-inflammatory cells suppress inflammation.
Atherosclerosis: Molecular Action And Suppression Of NKT Cell Subsets
Funder
National Health and Medical Research Council
Funding Amount
$458,815.00
Summary
Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed ....Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed towards understanding the role of a subset of while blood cells known as NKT cells in the inflammatory process. In particular we will examine whether the activity of NKT cells in promoting atherosclerosis can be controlled either by the administration of drugs that deprive them of molecules that stimulate their activity and-or by the injection of another population of white blood cells known as regulatory T cells that may to limit their activity. Our preclinical study of atherosclerosis in mice has potential for extension to the control of atherosclerosis in humans. Successful translation in this way can be expected to provide a significant health benefit.Read moreRead less
Investigation Of A New Leukocyte Recruitment Mechanism At Sites Of Vascular Injury
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Blood clots formed at sites of small vessel injury can cause damage of vital organs by obstructing blood flow and promoting a proinflammatory response by efficiently recruiting and activating leukocytes. The molecular mechanisms responsible for the latter event are poorly defined. We have established a new mouse model, gained novel insights into the leukocyte recruitment by blood clots, and aim to define the precise mechanism for this process in this application.
M2 Macrophage Polarization As A Cause Of Vascular Fibrosis And Stiffening In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$657,028.00
Summary
Blood vessel stiffening is a hallmark of hypertension (A.K.A. high blood pressure) and is thought to be a major contributor to the clinical complications of the condition, which include heart failure, stroke and renal impairment. Here we will test the novel concept that this stiffening process is caused by certain types of white blood cells (macrophages), which enter the walls of blood vessels and signal the surrounding cells to produce a rigid scaffolding protein called collagen.
Examining The Role Of Extracellular Myeloperoxidase In The Pathogenesis, Identification And Treatment Of High-risk Unstable And Ruptured Atherosclerotic Plaque
Funder
National Health and Medical Research Council
Funding Amount
$103,356.00
Summary
Vascular inflammation has emerged as a key driver and therapeutic target for stroke and heart attack. Existing diagnostic techniques and treatments do not target inflammation so that residual inflammatory risk remains. There is a need to identify patients with active inflammation who may benefit from treatment. Myeloperoxidase is an inflammatory enzyme abundant in plaque at risk of rupture and subsequent stroke or heart attack and presents as a potential diagnostic tool and therapeutic target.
B1a B Cells: Atheroprotective Mechanisms And Therapeutic Application
Funder
National Health and Medical Research Council
Funding Amount
$547,180.00
Summary
Atherosclerosis-related heart attacks and strokes remain leading causes of global deaths despite use of potent lipid-lowering drugs. Thus, another therapeutic option is urgently needed. Our laboratory found that B1a B cells protect against atherosclerosis. We will study the therapeutic efficacy of expanding B1a cells by different approaches in atherosclerosis. Our proposal for clinical translation is to reduce mortality from atherosclerosis-based heart attacks and strokes.