The long-term side effects of renal denervation are unknown. This project is designed to (1) investigate the potential atherosclerosis-promoting effect of renal denervation, and (2) to study the effectiveness of anti-inflammatory drugs to minimize this potential side effect. Ultimately, this project may improve the beneficial effects and minimize the potential side effects of renal denervation by routinely treating renal denervated patients with anti-inflammatory drugs.
Targeting Dysfunctional Mitochondria In Macrophages To Inhibit Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$1,009,796.00
Summary
The major contributing cells to heart disease are macrophages. These cells scavenge cholesterol, keeping the blood vessels clean and limiting heart disease. The macrophages must process and donate the scavenged cholesterol onto HDL-cholesterol that carries them back to the liver for removal. This process requires the powerhouse of the cell, the mitochondria to be functional. We have discovered that process fails and have novel drugs to re-instate this process of cholesterol removal.
S100A8/A9 As A Target In Metabolic Diseases To Inhibit The Acceleration Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$554,990.00
Summary
Obesity and diabetes are the leading cause of premature death, due to accelerated cardiovascular disease (CVD). The abundance of blood monocytes influences the progression and regression of CVD. We discovered that S100A8/A9 promotes monocyte production in obesity and diabetes. This project will explore how S100A8/A9 is produced in diabetes and obesity and if blocking its function using a novel drug will prevent obesity and diabetes associated CVD.
BAFF And Its Receptors:contribution And Therapeutic Potential In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Atherosclerosis is an inflammatory reaction to cholesterol in blood vessels. Despite cholesterol-lowering statins, atherosclerosis-based heart attacks and strokes remain a major cause of deaths. Studies of BAFF, a pro-inflammatory molecule can shed new light on the inflammation. As BAFF blockers are already in clinical trials to treat inflammatory diseases, our study has potential to lead to using BAFF blockers to treat human atherosclerosis.
Investigation Into The Intervention Of Arterial Thrombosis And Atherosclerosis Using Shear Sensitive Nanoparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$462,601.00
Summary
In this project we aim to provide a targeted therapy that inhibits atherosclerosis, in-stent restenosis and thrombosis; pathologies characterized by high shear stress due to a reduction in the vessel lumen. We will apply microfluidic technology to characterize lipid nano-capsules that are tagged with antibodies against activated platelets or VCAM-1, loaded with anti-platelet or immune suppressive drugs and are prone to rupture specifically under high shear stress conditions.
Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.
Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
Exploring The Therapeutic Potential Of TRAIL In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$446,374.00
Summary
TNF-related apoptosis-inducing ligand (TRAIL) is a protein with potentially useful actions in human health and disease. TRAIL is able to prevent atherosclerosis, the cause of heart attacks and strokes. In addition, we have recently shown that its actions on fat and the pancreas may prevent the development of the metabolic syndrome and type 2 diabetes. These studies will explore the therapeutic potential of TRAIL for the prevention of diabetes and heart disease in a range of animal models.
Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
ABCA12 – A New Regulator Of Cellular Lipid Metabolism And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$786,676.00
Summary
Dysregulation of cholesterol metabolism plays a key role in a number of diseases – from diabetes and atherosclerosis to neurological and skin disorders. Mechanisms of regulation of cholesterol metabolism are poorly understood. We have recently discovered a new pathway regulating cholesterol metabolism and in this study we will investigate molecular, cellular and physiological mechanisms of this pathway and will identify the possibilities to target it for therapeutic intervention.