Distribution of macrophage polarization markers in human atherosclerosis.
OBJECTIVE
Macrophages are decisive in the chronic inflammatory processes that drive atherogenesis. The purpose of this study was to explore the presence and spatial distribution of polarized macrophage populations in human atherosclerosis.


RESULTS
We used transcriptomics and immunohistochemistry to analyze macrophage subset dynamics in successive stages of atherogenesis. Developing lesions progressively accumulated both M1 and M2 cells, as was signified by the enhanced expression of associated markers at the transcriptional and protein level. Histologically, these markers were confined to overlapping, but spatially distinct CD68(+) areas of the intima. We subsequently quantified the presence of these markers in relation to morphological determinants of plaque stability. In line with their pro-inflammatory characteristics, M1 macrophages dominated the rupture-prone shoulder regions of the plaque over M2 polarized cells, while the fibrous caps of lesions showed no significant differences between subsets. In contrast, vascular adventitial tissue displayed a pronounced M2 activation profile. As expected, areas of intraplaque hemorrhage clearly associated with CD163 staining. Rather than being limited to complicated lesions, this M2 marker was also readily detectable in stable plaques. Finally, foamy macrophages displayed an ambiguous repertoire that incorporates individual M1 and M2 markers.


CONCLUSIONS
M1 and M2 macrophage populations are present throughout atherogenesis. These subsets display disparity when it comes to their prevalence in morphological compartments of the vessel wall. Our current findings warrant continued investigation into the functional implications of polarized macrophage populations in human atherosclerosis.
Dept. of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, 6229ER Maastricht, The Netherlands.
J Lauran
JL
Stöger
Marion J J
MJ
Gijbels
Saskia
S
van der Velden
Marco
M
Manca
Chris M
CM
van der Loos
Erik A L
EA
Biessen
Mat J A P
MJ
Daemen
Esther
E
Lutgens
Menno P J
MP
de Winther
D063194:Adventitia / Q000276:immunology / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000276:immunology* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000473:pathology; D008297:Male; D058226:Plaque, Atherosclerotic; D012333:RNA, Messenger / Q000032:analysis; D012422:Rupture, Spontaneous; D012720:Severity of Illness Index; D059467:Transcriptome
D015415:Biomarkers; D018836:Inflammation Mediators; D012333:RNA, Messenger