SP2 - SYMPATH
Experimental modeling and mechanistic analysis of pneumonia-aggravated atherosclerosis
In subproject 2 of the SYMPATH consortium, the data of clinical cohorts of patients with atherosclerotic coronary heart disease and pneumonia will be supplemented and compared with data from studies on experimental atherosclerosis and pneumonia models. The aim of this approach is to investigate pneumonia-associated mechanisms of disease development in atherosclerosis and acute coronary syndrome. These questions cannot be answered by purely clinical investigations because they take place before the diagnosis is made or no adequate tissue samples from patients are available. Therefore, mechanistic analyses require the creation and validation of mathematical models, which will be carried out in subproject 3. These analyses will also be complemented by manipulations of biological signaling pathways. A series of experiments will generate comprehensive longitudinal data on the effects of bacterial or viral pneumonia on the development of atherosclerosis in standardized mouse models. The experimental models are designed to map the clinical course of atherosclerosis after pneumonia. Initial experiments will provide the basic information for the mathematical modelling of disease mechanisms. With increasing progress in mathematical modelling in subproject 3, the experimental investigations will focus on questions and hypotheses resulting from the modelling. Accordingly, further experiments will focus on signaling pathways and specific pathogen and host factors, depending on the hypothesis, in order to work out their significance as possible therapeutic approaches in the translational approach. The results of these investigations are then used in an iterative process for modelling.