Abstract 12255: Noninvasive Molecular Imaging of Differential Endothelial Adhesion Molecule Expression in Early Atherosclerosis Correlates With Plaque Macrophage Content in Apo E Knockout Mice
Introduction: Targeted microparticles of iron oxide (MPIO) can detect endothelial inflammation in advanced mouse atherosclerosis by ex vivo magnetic resonance imaging (MRI). However, the sensitivity of MPIO for non-invasive detection of early endothelial activation has not been established.
Hypothesis: MPIO targeting both P-selectin and VCAM-1 can detect endothelial activation in early mouse atherosclerosis by in vivo MRI.
Methods: MPIO (1 μm) were conjugated to P-selectin and VCAM-1 monoclonal antibodies (50:50) (PV-MPIO) or IgG-1 control (IgG-MPIO). Female apoE −/− mice fed standard chow diet for 8, 14, 20 and 30 weeks underwent in vivo MRI (9.4 Tesla) of the aortic root using a T2*-weighted 3D gradient-echo sequence (resolution 100 μm3). Following a baseline scan, mice were administered PV-MPIO or IgG-MPIO (3.3 mg iron per kg) and post-contrast T2*-weighted datasets acquired at 20 and 60 min. Aortic root MPIO binding was quantified by MRI and histology, and lesion macrophage content assessed by immunohistochemistry.
Results: MRI showed significant aortic root PV-MPIO binding at 20 min (P<0.001) and 60 min (P<0.001) post-injection. At 8 weeks, little PV-MPIO binding was observed (0.17 ± 0.08 vs 0.14 ± 0.07 mm2 (n = 4) at baseline). PV-MPIO signal area (mm2) increased 3.5-fold at 14 weeks (0.56 ± 0.21 (n = 6) vs 8 weeks) (P<0.05) and 2.6-fold at 20 weeks (1.44 ± 0.09 mm2 (n=7)) (Fig A) vs 14 weeks (P<0.01), but reduced 2-fold by 30 weeks (0.71 ± 0.06 (n=7) vs 20 weeks (P<0.01)) (mean ± SEM). No IgG-MPIO binding was observed (0.11 ± 0.11 (n = 6)) (Fig B). By histology, similar patterns of PV-MPIO binding (Fig C) and lesion macrophage area (Fig D) over time were found. Lesion macrophage area significantly correlated with PV-MPIO binding assessed by MRI (P = 0.001) and histology (P = 0.015).
Conclusions: MPIO targeting both P-selectin and VCAM-1 enabled rapid in vivo assessment of endothelial activation in early atherosclerosis, which correlated with lesion macrophage content.
- © 2010 by American Heart Association, Inc.