Chapters authored
The 18 kDa Translocator Protein and Atherosclerosis in Mice Lacking Apolipoprotein E
Part of the book: Lipid Metabolism
Thrombosis, Atherosclerosis and Atherothrombosis – New Insights and Experimental Protocols
Previous studies have shown that TSPO as well as apolipoprotein E (Apo E) can be associated with processes such as cholesterol metabolism, oxidative stress, apoptosis, glial activation, inflammation, and immune responses. As a ligand for cell-surface lipoprotein receptors, apolipoprotein E can prevent atherosclerosis by clearing cholesterol-rich lipoproteins from plasma. Furthermore, TSPO takes part in the regulation of gene expression for proteins involved in adhesion, which potentially may play a role in platelet aggregation. There are indications that the Apo E protein is involve in platelet aggregation, while TSPO platelet levels have been found to be increased with various neurological disorders, in particular, in stress-related disorders. The role of platelets in atherogenesis and the potential therapeutic impact of TSPO ligands on disease prevention are of great interest. To determine TSPO binding characteristics in this paradigm, we applied binding assays with [3H]PK 11195 on isolated platelets and erythrocyte membranes. The in vivo findings in Apo E knockout mice revealed that TSPO levels appear to be enhanced in platelets and erythrocytes of Apo E knockout mice, and thus suggest that TSPO and Apo E expression may be interconnected in relation to some aspect of the host defense response. Other organs tested, such as liver, testis, brain, heart, aorta, lung, kidney and spleen, did not show a difference in TSPO binding levels between Apo E knockout mice and wild-type mice. This suggests that TSPO levels may be part of a feedback control system for steroid production (responding to alterations in steroid levels), rather than being regulated by a feed-forward signal provided by cholesterol (i.e. TSPO levels in relation to steroidogenesis are not being regulated by cholesterol levels in vivo).
Part of the book: Thrombosis, Atherosclerosis and Atherothrombosis