GENIUS and IN-CONTROL in transition; a novel ex-vivo based model system to study atherosclerosis

Atherosclerosis, the main cause of cardiovascular disease, is a chronic inflammatory disease caused by the accumulation of inflammatory cells and cholesterol in the vessel wall. The atherosclerotic plaque, which is caused by this inflammatory reaction, can grow to such an extent that it can completely block the artery. In addition, the plaque can rupture and cause a blood clot, possibly resulting in a heart attack or stroke. Various organs in the body play a role in the development of atherosclerosis, which is why the underlying mechanisms of this disease are often studied in laboratory animals. However, the data obtained from these studies cannot always be directly translated to humans. In this project, we therefore set the goal of developing a new ex vivo model based on atherosclerotic plaque from humans, in which candidate drugs that counteract atherosclerosis can be tested. For the development of this model, we used atherosclerotic plaque material from patients undergoing an endarterectomy. The patients undergo this surgery to remove an advanced atherosclerotic plaque from the carotid artery, often after these patients have had a stroke. This plaque is cut into precise slices of 2 mm thickness, after which these slices are placed in a culture dish. We managed to keep these slices alive for more than 10 days, so that we could test candidate drugs on them. Several anti-inflammatory drugs that are in development for use in cardiovascular disease have been tested in this new model system. In line with the goals set in the Transition to Animal-Free Innovation (TPI) initiative, this model will therefore be able to lead to a reduction in the number of laboratory animals used in cardiovascular research, and the results obtained from these studies will be directly translatable to the patient.