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Understanding the Role of Cytomegalovirus in Atherosclerosis through Metabolic Pathway Modeling

This study explores the complex interplay between cytomegalovirus (HCMV) and atherosclerosis, a leading cause of death characterized by inflammation and cholesterol imbalance. We build an interaction map to visualize the relationship between lipid metabolism, immune response, and inflammatory pathways influenced by HCMV. Key processes involving liver X receptors (LXRs), peroxisome proliferator-activated receptors (PPARs), and Rho proteins are examined. The role of statins in lowering atherosclerotic risk and limiting HCMV infection is also discussed, with potential software tools and statistical methods developed to further the research.

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Understanding the Role of Cytomegalovirus in Atherosclerosis through Metabolic Pathway Modeling

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Presentation Transcript

  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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