The dark side of innate immune memory: the development of atherosclerosis

Cardiovascular diseases, specifically atherosclerosis, are the leading cause of death worldwide. In the Netherlands alone, each year 100 people die from atherosclerosis. It is important to better understand the progression of this disease. In the last 15 years, the role of inflammation and the immune system in atherosclerosis has been highlighted. The most important immune cells playing a role in atherosclerosis are monocytes. Monocytes are part of the innate immune system, which is rapid, aspecific and without any memory. The other immune system is called adaptive, and can obtain a memory by producing memory cells. Recently, it was discovered that this dichotomy is not true. Also monocytes can develop memory after a first encounter with a ‘bad particle’, after which the cell is turning hyperactive. There is no memory cell made here, the cell itself will become different. In my thesis, I studied the role of inflammation in the process of atherosclerosis with these new findings. I studied whether some forms of cholesterol can make monocytes hyperactive. And whether monocytes of patients with atherosclerosis are also hyperactive. Thirdly, I tried to unravel the mechanisms of this hyperactivity, in order to develop new drugs in the futur