Dr Julie Proudfoot
Scientific Officer, Cell Biology & Imaging Platform, Technical Services, The University of Western Australia
Research Overview
Coronary heart disease involves narrowed coronary arteries, and atherosclerosis is the major underlying mechanism. Atherosclerotic plaques in artery walls develop due to high lipid levels and inflammation. Macrophages have numerous functions, including removing dead cells and being part of the immune system. To carry out their various functions, macrophages need to migrate. Dr Proudfoot previously showed that an oxidized lipid, F2-isoprostane, found in atherosclerotic plaques, stimulates macrophage migration.
Macrophage migration through tissues requires degradation of surrounding matrix through macrophage release of enzymes and plays an important role in inflammation and atherosclerosis.Colchicine is a widely available drug with anti-inflammatory properties, commonly used for the treatment of gout. More recently, it has been re-purposed and shown to reduce the risk of cardiovascular events in patients with recent heart attacks. The mechanism by which colchicine reduces inflammation remains incompletely understood.
With the support of a grant from the RPH Research Foundation in 2019, Dr Proudfoot discovered that F2-isoprostane significantly inhibited mouse macrophage matrix degradation. This led to the investigation of matrix degradation in human macrophages, using time-lapse imaging with the RPH-RF fluorescence microscope. Human macrophages were isolated from buffy coats provided by the Australian Red Cross Lifeblood. Dr Aaron Magno from the RPH Research Centre greatly assisted with isolating and growing macrophages and time-lapse imaging with the fluorescence microscope.
The reduction in secondary cardiovascular events following colchicine treatment led to examination of the effect of colchicine on human macrophage matrix degradation. Low dose colchicine significantly reduced human macrophage matrix degradation, suggesting this may contribute to the favourable treatment outcomes.
More knowledge about the interaction between macrophages and the extracellular matrix is needed to understand tissue remodelling in the heart before and after a heart attack. The potential effect of colchicine on tissue remodelling requires further investigation.