M1-Activated Macrophages Migration, A Marker of Aortic Atheroma Progression A Preclinical MRI Study in Mice

Background: M1-activated Macrophages (M1M) play a major role in atherosclerotic lesions of aortic arch, promoting proinflammatory response. In vivo trafficking of M1M in aortic plaques is therefore critical. Methods: M1M from bone marrow cell culture were magnetically labeled, using iron nanoparticles, intravenously injected and followed up with 3 day magnetic resonance imaging (MRI) in mice developing macrophage-laden atheroma (ApoE2 knock-in mice). M1M recruitment in aortic arch lesions was assessed both by MRI and histology. Results: In all ApoE2 knock-in mice injected with labeled cells, high resolution MRI showed localized signal loss regions in the thickened aortic wall, with a maximal effect at day 2 (-34% +/- 7.3% P < 0.001 compared with baseline). This was confirmed with Prussian blue (iron) staining and corresponded to M1M (Major Histo-compatibility Complex II positive). Clear different intraplaque and adventitial dynamic distribution profiles of labeled cells were observed during the 3 days. Conclusion: M1M dynamic MRI is a promising marker to noninvasively assess the macrophage trafficking underlying aortic arch plaque progression.