Bioenergetics of macrophages in atherosclerosis

Years funded:
2018 - 2019

Macrophages are a type of white blood cell that promotes atherosclerosis, a build-up of fatty lesions in the vessel wall that leads to heart attacks and strokes. 

Macrophages have many functions and can be broadly classified as inflammatory (M1) and anti-inflammatory (M2). Current dogma suggests that M1s play a pathogenic role in atherosclerosis while promoting an M2 phenotype will resolve atherosclerotic lesions. Dr Man Lee has strong data suggesting that this scenario is an oversimplification and indeed may be incorrect. 

Dr Lee shows that M2s are the predominant macrophages in human and mouse lesions due to the cell’s failure to promote cholesterol efflux. Furthermore, restoring mitochondrial function of macrophages restores cholesterol efflux capacity in human cell culture experiments and mouse models of atherosclerosis. 

Macrophages come from a circulating pool of blood monocytes (3 subsets) and Dr Lee discovered that a particular human subset (non-classical) is responsible for foam cell formation. 

Mouse monocytes only have 2 subsets and thus it is difficult to translate findings from atherosclerotic mouse models into the human setting. Thus, to overcome this major defect in murine research, Dr Lee pioneered a humanised (human blood cells) mouse model of atherosclerosis that consists of the 3 human monocyte subsets. 

Dr Lee will use this model to determine the contribution of human monocyte subsets to CVD, and whether mitochondrial interventions can be used to combat atherosclerosis.

Researcher Profile

Dr Man Lee

Institute: Baker Heart and Diabetes Institute
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