Abstract 14431: Global Loss of Id3 Leads to Increased Atherosclerosis in Western-Fed LDL Receptor Knockout Mice and Decreased Aortic B Lymphocyte Density on Optical Imaging
Background: Recent novel findings identified the helix-loop-helix transcription factor Inhibitor of Differentiation-3 (Id3) as essential for B lymphocyte-mediated atheroprotection in ApoE−/− mice. However, whether Id3 modulates aortic B cell density and atherosclerosis independent of genetic background is unknown.
Hypothesis: Global loss of Id3 leads to decreased aortic B cell density and an increase in atherosclerosis in LDLr−/− mice.
Methods: Aortas were harvested from chow fed Id3+/+ LDLr−/− (LDLr), Id3−/− LDLr−/− (DKO), and B cell-deficient muMT (muMT) mice on a C57BL/6 background and incubated with Cy5.5-labeled anti-CD19 antibody to identify B cells with near-infrared fluorescent imaging. Eight week-old LDLr mice, Id3+/− LDLr−/− (Het) mice, and DKO mice were fed either Western or chow diet. After either 8 or 16 weeks, serum lipid levels were measured, the aortas were harvested, and percent aortic atherosclerosis was determined by en face Sudan IV staining.
Results: Optical imaging (Figure) demonstrated a significant 28% increased fluorescence in LDLr aortas compared with muMT controls (p<0.002) while there was only a 13% increase in DKO aortas (<0.03) with a significant difference between all groups. There were no significant differences in lipid levels between LDLr and DKO mice regardless of diet. There was no significant difference in the development of atherosclerosis in chow-fed animals after either 8 or 16 weeks. Western-fed DKO mice developed significantly more atherosclerosis than LDLr mice after 8 weeks (p<0.002). There was a significant difference in atherosclerosis between all groups at 16 weeks of Western diet (DKO 13.9%, Het 8.8%, LDLr 6.9%, p<0.002).
Conclusions: LDLr−/− mice null for Id3 have reduced aortic B cell density prior to Western feeding with a subsequent significant increase in the development of atherosclerosis after Western feeding.
- © 2010 by American Heart Association, Inc.