Research reveals the liver's immune system consumes the "bad cholesterol"

Cholesterol is a type of fat that is essential for many functions in the body, such as making hormones and cell membranes. However, too much cholesterol in the blood can be harmful, as it can stick to the walls of the arteries and form plaques that narrow or block the blood flow. This results in atherosclerotic cardiovascular disease, the primary underlying cause of heart attacks and strokes, and the leading cause of death worldwide.

In the study, researchers tried to understand how different tissues in the body react to high levels of LDL, also called ‘bad cholesterol’, in the blood. To test this, they created a system where they could quickly increase the cholesterol in the blood of mice.

“Essentially, we wanted to detonate a cholesterol bomb and see what happened next. We found that the liver responded almost immediately and removed some of the excess cholesterol,” said Stephen Malin, lead author of the study and principal researcher at the Department of Medicine, Solna, Karolinska Institute.

However, it wasn’t the typical liver cells that responded, but a type of immune cell called Kupffer cells that are known for recognising foreign or harmful substances and eating them up.

“We were surprised to see that the liver seems to be the first line of defence against excess cholesterol and that the Kupffer cells were the ones doing the job. This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.” Said Malin.

“Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis. This could help us develop more holistic and effective strategies to combat this common and deadly disease.”

Reference: Giada Di Nunzio, Sanna Hellberg, Yuyang Zhang, Osman Ahmed, Jiawen Wang, Xueming Zhang, Hanna M. Björck, Veronika Chizh, Ruby Schipper, Hanna Aulin, Roy Francis, Linn Fagerberg, Anton Gisterå, Jari Metso, Valentina Manfé, Anders Franco-Cereceda, Per Eriksson, Matti Jauhiainen, Carolina E. Hagberg, Peder S. Olofsson & Stephen G. Malin; Journal: Nature Cardiovascular Research; DOI: 10.1038/s44161-024-00448-6