Translocator protein localises to CD11b+ macrophages in atherosclerosis
Autor: | Arvind Parmar, Victoria Lee, Andrew Arthur, Jeremy Szajer, Elvis Pandzic, Kerry-Anne Rye, William J. Ryder, Sandra Fok, Chantal Kopecky, Renee Whan, Blake J. Cochran, Alexander Dupuy |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Translocator protein DAPI Receptor Foam cell biology business.industry Monocyte medicine.disease 030104 developmental biology medicine.anatomical_structure chemistry Integrin alpha M biology.protein Antibody Cardiology and Cardiovascular Medicine business Infiltration (medical) Artery |
Zdroj: | Atherosclerosis. 284:153-159 |
ISSN: | 0021-9150 |
Popis: | Background and aims Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. The purpose of this study was to determine if the TSPO ligand, 18F-PBR111, can identify early atherosclerotic lesions and if TSPO expression can be used to identify distinct macrophage populations during lesion progression. Methods ApoE−/− mice were maintained on a high-fat diet for 3 or 12 weeks. C57BL/6J mice maintained on chow diet served as controls. Mice were administered 18F-PBR111 intravenously and PET/CT imaged. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, and fluorescently labelled with antibodies to TSPO, the tissue resident macrophage marker F4/80 and the monocyte-derived macrophage marker CD11b. TSPO expression and the macrophage markers were visualised in fatty streaks and established plaques by light sheet microscopy. Results While tissue resident F4/80 + macrophages were evident in the arteries of animals without atherosclerosis, no CD11b + macrophages were observed in these animals. In contrast, established plaques had high CD11b and low F4/80 expression. A ∼3-fold increase in the uptake of 18F-PBR111 was observed in the aortas of atherosclerotic mice relative to controls. Conclusions Imaging of TSPO expression is a new approach for studying atherosclerotic lesion progression and inflammatory cell infiltration. The TSPO ligand, 18F-PBR111, is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans. |
Databáze: | OpenAIRE |
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