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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

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


Atherosclerosis
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.


Lxrs ppars and rho proteins
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.


The case study
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.


Possible ways for me to contribute
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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