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Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis

Bird, J. L. E., Izquierdo-Garcia, D., Davies, J. R., Rudd, J. H. F., Probst, Katrin C., Figg, N., Clark, J. C., Weissberg, P. L., Davenport, A. P. and Warburton, E. A. 2010. Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis. Atherosclerosis 210 (2) , pp. 388-391. 10.1016/j.atherosclerosis.2009.11.047

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Abstract

Macrophage presence within atherosclerotic plaque is a feature of instability and a risk factor for plaque rupture and clinical events. Activated macrophages express high levels of the translocator protein/peripheral benzodiazepine receptor (TSPO/PBR). In this study, we investigated the potential for quantifying plaque inflammation by targeting this receptor. TSPO expression and distribution in the plaque were quantified using radioligand binding assays and autoradiography. We show that cultured human macrophages expressed 20 times more TSPO than cultured human vascular smooth muscle cells (VSMCs), the other abundant cell type in plaque. The TSPO ligands [3H](R)-1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([3H](R)-PK11195) and [3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]-DAA1106) bound to the same sites in human carotid atherosclerotic plaques in vitro, and demonstrated significant correlation with macrophage-rich regions. In conclusion, our data indicate that radioisotope-labelled DAA1106 has the potential to quantify the macrophage content of atherosclerotic plaque.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0021-9150
Date of First Compliant Deposit: 15 December 2016
Date of Acceptance: 25 November 2009
Last Modified: 31 Jan 2020 04:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/96505

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