A Stochastic Petri Net-Based Model of the Involvement of Interleukin 18 in Atherosclerosis |
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| Authors: | Dorota Formanowicz,Agnieszka Rybarczyk,Marcin Radom,Krzysztof Tana ,Piotr Formanowicz |
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| Affiliation: | 1.Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland; ;2.Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; (A.R.); (M.R.); (K.T.);3.Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland;4.Faculty of Electrical Engineering, Gdynia Maritime University, 81-225 Gdynia, Poland |
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| Abstract: | Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine with pleiotropic properties, which is involved in T and NK cell maturation and the synthesis of other inflammatory cytokines and cell adhesion molecules. It plays a significant role in orchestrating the cytokine cascade, accelerates atherosclerosis and influences plaque vulnerability. To investigate the influence of IL-18 cytokine on atherosclerosis development, a stochastic Petri net model was built and then analyzed. First, MCT-sets and t-clusters were generated, then knockout and simulation-based analysis was conducted. The application of systems approach that was used in this research enabled an in-depth analysis of the studied phenomenon. Our results gave us better insight into the studied phenomenon and allow revealing that activation of macrophages by the classical pathway and IL-18-MyD88 signaling axis is crucial for the modeled process. |
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| Keywords: | atherosclerosis inflammation mathematical modeling Petri net stochastic Petri net t-invariants |
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