Novel and Emerging Technologies (NET) Grant (PhD studentship)
Prof David Firmin and Dr Andrew Scott, Royal Brompton Hospital and Imperial College London
Atherosclerosis involves the accumulation of fatty deposits in the walls of major arteries and is the underlying cause of both coronary heart disease and stroke. Initially, the fat accumulates within white blood cells, called macrophages, which enter the artery wall in response to chemical damage. The fat is taken up from low density lipoproteins or LDL – the so-called ‘bad’ cholesterol – which is recognised by specific receptors on the surface of the macrophages. This can be reversed when the fat is removed from the cell, via different receptors, and transported to the liver by high density lipoprotein or HDL – the so-called ‘good’ cholesterol. These processes are dependent on the activity of particular genes which code for the receptors and enzymes involved, and the balance between the two processes determines the rate at which atherosclerosis develops.
Recent evidence suggests that a class of small RNA molecules, called microRNA, regulates the activity of clusters of genes involved in different processes within the human body. The aim of this project is to investigate microRNAs that regulate genes involved in atherosclerosis and to see if their activity can be altered to slow or even reverse the accumulation of fat in the artery wall. Using human macrophages, the research will investigate the ability of two microRNAs to regulate fat build-up in these white blood cells, and whether inhibitors or mimics of these molecules can alter fat accumulation.
Despite substantial decreases in deaths from cardiovascular disease over the last two decades, coronary heart disease and stroke are still major causes of morbidity and mortality in the UK. Also, the rise in the numbers of people who are overweight or obese is expected to cause considerable healthcare problems in the future. This project explores the exciting idea that the development of atherosclerotic plaques in arteries may be altered by microRNAs, and that mimics or inhibitors of these molecules may lead to treatments to prevent, or even reverse, atherosclerosis.