Abstract
Abstract Macrophages are central to the development of atherosclerosis. Folate-receptor positive (FR+) macrophages have been reported to orchestrate inflammatory processes in multiple inflammatory diseases, but the role of FR+ macrophages in atherosclerosis is unknown. Here, we report the use of folate to target radioactive and fluorescent imaging agents to macrophages present within aortas of atherosclerotic ApoE-/- mice. Folate-targeted 99m-Tc and folate-DyLight680 were synthesized and injected into ApoE-/- mice that were fed either normal or Western chow for 25 weeks. Mice and their excised aortas were then imaged to assess accumulation of both folate conjugates. Flow cytometric analysis of single cell suspensions of collagenase-digested aortas was also performed. Folate-targeted compounds, but not nontargeted compounds, were found to accumulate in atherosclerotic lesions of ApoE-/- mice, with greater uptake in mice fed Western chow than normal chow. The targeted cells were also confirmed to be FR+ macrophages. These data demonstrate that FR+ macrophages are present in atherosclerotic lesions and that they can be targeted with folate-conjugated compounds. Folate targeting could conceivably be developed for the staging of atherogenesis and treating of the associated disease.
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