Modulation of genes involved in inflammation and cell death in atherosclerosis-susceptible mice

Zadelaar, Anna Susanne Maria (2006)

Doctoral Thesis

In this thesis we focus on atherosclerosis as the main cause of cardiovascular disease. Since inflammation and cell death are important processes in the onset and progression of atherosclerosis, we investigate the role of several genes involved in inflammation and cell death in the vessel wall and their effect on atherosclerosis. We use several ways to modulate gene expression. Examples from different chapters are whole body deletion of TNF (2), local gene targeting of Fas Ligand to the cap of the plaque (3), conditional gene targeting of mdm2, thereby upregulating p53 (4), and beta-galactosidase (5), and pharmacological targeting of PPARs (6). In this thesis we use various mouse models of atherosclerosis, such as the apoE deficient mouse, the "humanized" apoE3*Leiden mouse and accelerated atherosclerosis induced by collar placement.

• Atherosclerosis
• Mice
• Inflammation
• Cell death
• Genes
• TNFalpha
• FasLigand
• MDM2
• Rosa26
• PPARagonists

• All authors: Zadelaar, Anna Susanne Maria
• Supervisor: Havekes, L.M.
• Co-supervisor: Vlijmen, B.J.M. van
• Qualification: Doctor (dr.)
• Awarding Institution: Department of Cardiology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2006-03-23
• ISBN (print): 9064644918
• Sponsorship: TNO-Quality of life, The Gaubius Laboratory, Netherlands Organization of Scientific Research(NWO/ZonMW), Astra Zeneca, Sweden, Leids Universitair Fonds (LUF)