Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis |
| |
Authors: | JLE Bird D Izquierdo-Garcia JR Davies JHF Rudd KC Probst N Figg JC Clark PL Weissberg AP Davenport EA Warburton |
| |
Institution: | 1. Clinical Pharmacology Unit, Addenbrooke''s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom;2. Wolfson Brain Imaging Centre, Addenbrooke''s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom;3. Division of Cardiovascular Medicine, Addenbrooke''s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom;4. Clinical Neurosciences, University of Cambridge, Addenbrooke''s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|