Atherosclerosis is a common condition in which an accumulation of fat, named “plaque” builds up on the innermost walls of arteries, causing them to become narrow and restrict the blood flow to vital organs such as the heart and the brain. It can be life-threatening if untreated – narrow arteries increase the risk of a blockage and lead to a heart attack or stroke.
Macrophages are immune cells that play essential roles in organ homeostasis as well as infection and injury. Key to their success is the ability to alter their transcriptional patterns of gene expression to perform highly-specialised roles in specific organs and tissues. However, their prominent role means that when things go wrong, macrophages can be impactful drivers of disease.
In atherosclerosis, macrophages can transform into the fat-laden “foam” cells, which are also known as lipid-associated macrophages (LAMs) and are a hallmark of atherosclerosis and other diseases, such as obesity and neurological diseases. Foam cells have been recreated in vitro and are thought to become activated perpetuating inflammation in the artery wall and this inflammation contributes to disease progression. Atherosclerosis can therefore be considered a lipid-driven inflammatory disease and targeting inflammation has been shown to improve cardiovascular outcomes for patients.
However, the inflammatory origin of atherosclerosis remains a mystery. If atherosclerosis involves lipid-driven inflammation, signatures of inflammation should be found on foamy macrophages within the plaques, but nothing had been found so far, leading to significant controversy in the field. The Kennedy scientists aimed to find these patterns and used unbiased single cell biology approaches on over 22,000 immune cells from the plaques of patients who had undergone surgical carotid atherosclerosis removal.