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Published on: February 20, 2019
M1-activated macrophages migration, a marker of aortic atheroma progression: a preclinical MRI study in mice
Amine Bessaad1, Monica Sigovan, Hasan Alsaid
1CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, University Lyon 1, Villeurbanne Cedex, France.
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.
Insights
Magnetic resonance imaging (MRI) noninvasively tracks M1-activated macrophages (M1M) in atherosclerotic plaques. This technique reveals dynamic macrophage trafficking within aortic arch lesions, aiding in understanding plaque progression.
Area of Science:
- Cardiovascular Research
- Immunology
- Medical Imaging
Background:
- M1-activated macrophages (M1M) are key drivers of inflammation in atherosclerotic lesions of the aortic arch.
- Understanding the in vivo movement of M1M within aortic plaques is crucial for studying disease progression.
Purpose of the Study:
- To develop and validate a noninvasive method for assessing M1M trafficking in atherosclerotic lesions.
- To utilize magnetic resonance imaging (MRI) to track M1M dynamics in the aortic arch.
Main Methods:
- M1-activated macrophages (M1M) were magnetically labeled with iron nanoparticles.
- Labeled M1M were intravenously injected into ApoE2 knock-in mice with developing atheroma.
- M1M recruitment and distribution in aortic arch lesions were monitored using 3-day serial MRI and confirmed with histology (Prussian blue staining).
Main Results:
- High-resolution MRI detected localized signal loss in the aortic wall, indicating M1M accumulation, with maximal effect at day 2 (-34%).
- Histological analysis confirmed the presence of M1M (Major Histo-compatibility Complex II positive) in signal loss regions.
- Distinct dynamic distribution patterns of labeled M1M were observed within plaques and adventitia over 3 days.
Conclusions:
- Dynamic MRI of M1-activated macrophages (M1M) is a promising noninvasive tool.
- This imaging approach can assess macrophage trafficking, a key factor in aortic arch plaque progression.
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