Translocator Protein Localises To CD11b+ Macrophages In Atherosclerosis

Kopecky, C.; Pandzic, E.; Parmar, A.; Szajer, J.; Lee, V.; Dupuy, A.; Arthur, A.; Fok, S.; Whan, R.; Ryder, W. J.; Rye, K.-A.; Cochran, B. J.

doi:10.1101/494377

bioRxiv · 10.1101/494377

Translocator Protein Localises To CD11b+ Macrophages In Atherosclerosis

Kopecky, C.·Pandzic, E.·Parmar, A.·Szajer, J.·Lee, V.·Dupuy, A.·Arthur, A.·Fok, S.·Whan, R.·Ryder, W. J.·Rye, K.-A.·Cochran, B. J.

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Abstract

BackgroundAtherosclerosis 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.\n\nMethods and ResultsApoE-/- 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 mature lesions by light sheet microscopy. 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, mature 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.\n\nConclusionsImaging 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.

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Kopecky, C., Pandzic, E., Parmar, A., Szajer, J., Lee, V., Dupuy, A., Arthur, A., Fok, S., Whan, R., Ryder, W. J., Rye, K.-A., Cochran, B. J.. 2018-12-15. Translocator Protein Localises To CD11b+ Macrophages In Atherosclerosis. https://doi.org/10.1101/494377

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