Abstract 491: In Vivo Bioluminescence Imaging of Inducible Nitric Oxide Expression in Atherosclerosis
Objectives: Inducible nitric oxide (iNOS) is expressed by inflammatory and vascular smooth muscle cells in response to cytokine stimulation and participates in atherogenesis. In vivo bioluminescence imaging (BLI) offers a noninvasive method for the detection and quantification of iNOS expression in living mice. We studied BLI of iNOS expression in an accelerated model of murine atherosclerosis.
Methods: Seven transgenic iNOS-luciferase mice (5 diseased and 2 sham-operated mice) were studied. Macrophage-rich atherosclerotic lesions were induced in the left common carotid artery by ligation after treatment with high fat diet and streptozotocin-induced diabetes. iNOS expression was measured serially by noninvasive BLI. At day 14, direct in situ BLI was performed after exposing the carotid arteries and animals were sacrificed.
Results: BLI signal from the ligated carotid arteries was significantly higher at day 5 (Fig 1⇓) compared to the baseline (1.1±0.2 x104 vs. 0.6±0.2 x104 photons(p)/s, p=0.03) and increased further by day 14 (1.3±0.5 x104 p/s, p=0.003), but not in sham-operated mice (0.5±0.1 x104 p/s, p=0.6). The localization of the BLI signal to the injured left but not the uninjured right carotid artery was further confirmed by direct imaging of exposed vessels (Fig 1⇓).
Conclusions: BLI allows serial noninvasive monitoring and quantification of iNOS expression in mouse atherosclerotic lesions and may provide a valuable small animal system to monitor the atherogenic process as well as the response to therapeutic interventions in vivo.