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The role of inflammation in the pathogenesis, identification and treatment of vulnerable plaque

Dr James Nadel, Institution: University of New South Wales

2020 Health Professional Scholarship

Years funded: 2021-2023


Cardiovascular disease (CVD) is the leading cause of death in Australia and worldwide, encompassing a group of disorders that effect the heart and blood vessels. The most common outcome relating to CVD are heart attacks and strokes, which occur due to a reduction of blood flow to the heart and brain, respectively. The majority of heart attacks and strokes occur because of atherosclerosis, a progressive, multi-factorial disease of the arteries characterised by the accumulation of cholesterol and inflammatory cells. The disease culminates in the rupture of unstable plaque, which can lead to blood clots, abrupt vessel occlusion and the loss of blood supply to these vital organs.

In recent years vascular inflammation has emerged as a key driver and therapeutic target for stroke and heart attack. Existing diagnostic techniques and medical therapies do not specifically target inflammation so that residual inflammatory risk remains untreated and undetected. Therefore, there is a clinical need to identify patients with active vascular inflammation who may benefit from targeted treatment. Recent findings have demonstrated that myeloperoxidase (MPO), an inflammatory enzyme, is abundant in vulnerable and ruptured but not stable plaques, identifying MPO as a potentially ground-breaking diagnostic tool and therapeutic target. Similarly, the development of novel therapies that inhibit MPO have shown promising results in human studies and a capacity to stabilise vulnerable plaques in animal models.

This PhD will seek to further explore the utility of MPO in the identification and treatment of unstable atherosclerotic plaques. Initially I will seek to confirm the link between MPO activity and ruptured human plaque before examining MPO’s role as a novel non-invasive imaging biomarker of vulnerable plaque. Lastly, I will assess the efficacy of MPO inhibitors as a potential therapeutic target for plaque stabilisation.

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