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Michiel Schaap’s perspective

Case Study 1 Modeling of lipid genetic and metabolic pathways in response to infection and immune stimulation in order to understand the relation between cytomegalovirus and atherosclerosis. Michiel Schaap’s perspective. Atherosclerosis.

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Michiel Schaap’s perspective

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  1. Case Study 1Modeling of lipid genetic and metabolic pathways in response to infection and immune stimulation in order tounderstand the relation between cytomegalovirus and atherosclerosis Michiel Schaap’s perspective

  2. Atherosclerosis • Atherosclerosis is specific type of cardiovascular disease and the number one cause of death in the western world. • It has been shown that atherosclerosis is an inflammatory disease. • Cholesterol and its transportation agent low-density lipoprotein (LDL) play an important role in this inflammatory process Cytomegalovirus • Several studies have demonstrated a positive correlation between human cytomegalovirus (HCMV) and cardiovascular disease • The exact pathophysiological mechanisms have not yet been determined. • Suggestions have been made that HCMV modulates components of the lipid pathway when developing a viral infection.

  3. LXRs, PPARs, and Rho proteins • Liver X receptors (LXRs) and proliferator-activated receptors (PPARs) have been found to play an important role in cholesterol absorption and excretion • And studies have shown that activation of Rho proteins appear to be a common component in vascular disorders Statins • (HMG-CoA) reductase inhibitors are known as statins and proven to reduce the amount of athesclerotic disease. • This cardiovascular disease risk reduction is expected to be caused by its ability to lower the amount of cholesterol synthesis and Rho protein prenylation. • Statins have also been shown to limit HCMV infection in human endothelial cells.

  4. The case study • Understand the biochemical effect of HCMV infection in the context of atherosclerosis, by: • Building an interaction map that represents the cross talk between cholesterol and fatty acid biosynthesis, PPAR and LXR and the Rho protein prenylation pathway. • Using the constructed interaction map to understand the regulatory mechanisms and their consequences on immune response and the inflammatory pathway.

  5. Possible ways for me to contribute • Development or adjustment of the necessary software tools for literature mining and/or simulation. • Formalizing and executing statistical tests • Reporting achieved results

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