Modeling immune system control of atherogenesis

Abstract Motivation: Atherosclerosis is a disease that is present in almost all humans, typically beginning in early adolescence. It is a human disease broadly investigated, that is amenable to quantitative analysis. Oxidized low-density lipoproteins (LDLs) and their autoantibodies are involved in the development of atherosclerosis in animal models, but their role in humans is still not clear. Computer models may represent a virtual environment to perform experiments not possible in human volunteers that can provide a useful instrument for monitoring both the evolution of atherosclerotic lesions and to quantify the efficacy of treatments, including vaccines, oriented to reduce the LDLs and their oxidized fraction. Results: We report the application of an agent-based model to model both the immune response to atherogenesis and the atheromatous plaque progression in a generic artery wall. The level of oxidized LDLs, the immune humoral response with production of autoantibodies, the macrophages activity and the formation of foam cells are in good agreement with available clinical data, including the formation of atheromatous plaques in patients affected by hypercholesterolemia. Availability: The model is available at http://www.immunogrid.eu/atherogenesis/ Contact: francesco@dmi.unict.i