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.


CONCLUSIONS
M1M dynamic MRI is a promising marker to noninvasively assess the macrophage trafficking underlying aortic arch plaque progression.
Bessaad
Amine
A
CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, University Lyon 1, Villeurbanne Cedex, France.
Sigovan
Monica
M
Alsaid
Hasan
H
De Souza
Geneviève
G
Provost
Nicolas
N
Majd
Zouher
Z
Menager
Christine
C
Honnorat
Jèrôme
J
Lagarde
Florence
F
Nighoghossian
Norbert
N
Nataf
Serge
S
Canet-Soulas
Emmanuelle
E
D000818:Animals; D001018:Aortic Diseases / Q000175:diagnosis*; D053329:Apolipoprotein E2 / Q000235:genetics; D001161:Arteriosclerosis / Q000175:diagnosis*; D015415:Biomarkers; D055879:Gene Knock-In Techniques; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic
D053329:Apolipoprotein E2; D015415:Biomarkers