Abstract 12451: Molecular Imaging Demonstrates Id3 Modulates B Lymphocyte Homing to Atherosclerosis-Prone Regions of the Aorta
Background: Id3 is a helix-loop-helix transcription factor expressed in mature B lymphocytes and implicated in B-lymphocyte-mediated atheroprotection. Yet region-specific homing of B lymphocytes to the aorta and the role of Id3 in this process is unknown.
Hypothesis: Loss of Id3 reduces B cell homing to atherosclerosis-prone regions of the aorta as shown by molecular imaging.
Methods: Aortas were harvested from chow fed Id3+/+ ApoE-/- (ApoE), Id3-/- ApoE-/- (DKO), and B cell-deficient muMT ApoE-/- (muMT) mice without atherosclerosis and incubated with Cy5.5-labeled anti-B220 antibody to identify B cells with near-infrared fluorescent imaging. Splenic B cells were isolated with 99% purity, labeled with indium-111 oxine, and 1X107 ApoE or DKO B cells were adoptively transferred to muMT recipient mice via tail vein injection. Control muMT mice received an injection of indium-111 oxine. After 20 hours, the aortas were harvested, underwent phosphor imaging and subsequent gamma well counting with adjustment for injected radioactive dose.
Results: Optical imaging demonstrated a significant 42% increased fluorescence in ApoE aortas compared with muMT controls (p<0.0002) while there was only a 15% increase in DKO aortas (<0.05) with a significant difference between all groups (<0.0001). Phosphor imaging (Figure 1) demonstrated a significant 290% signal intensity increase in ApoE aortas compared with control while DKO aortas had a 100% increase with a significant difference between all groups. Optical imaging and phosphor imaging showed greater signal present in the arch and abdominal aorta for both groups relative to the descending thoracic aorta.
Conclusion: B lymphocytes home to atherosclerosis-prone regions of non-diseased aorta. Consistent with a role for Id3 in promoting B lymphocyte-mediated atheroprotection, molecular imaging demonstrated that loss of Id3 decreased aortic B cell density and reduced B cell homing to these atherosclerosis prone regions.
- © 2010 by American Heart Association, Inc.