Distribution of macrophage polarization markers in human atherosclerosis

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. We used transcriptomics and immunohistochemistry to analyze macrophage...

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Vydáno v:	Atherosclerosis Ročník 225; číslo 2; s. 461 - 468
Hlavní autoři:	Stöger, J. Lauran, Gijbels, Marion J.J., van der Velden, Saskia, Manca, Marco, van der Loos, Chris M., Biessen, Erik A.L., Daemen, Mat J.A.P., Lutgens, Esther, de Winther, Menno P.J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Amsterdam Elsevier Ireland Ltd 01.12.2012 Elsevier
Témata:	Adventitia Adventitia - immunology Adventitia - pathology Aged Aged, 80 and over analysis atherogenesis atherosclerosis Atherosclerosis (general aspects, experimental research) Biological and medical sciences Biomarkers Biomarkers - analysis Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Cardiovascular system Carotid Arteries Carotid Arteries - immunology Carotid Arteries - pathology Carotid Artery Diseases Carotid Artery Diseases - genetics Carotid Artery Diseases - immunology Carotid Artery Diseases - pathology classification Coronary artery disease Disease Progression Female Fibrosis Foam cell Gene Expression Profiling Gene Expression Regulation genetics hemorrhage Human pathology Humans Immunohistochemistry immunology Inflammation Mediators Inflammation Mediators - analysis Innate immunity Macrophages Macrophages - classification Macrophages - immunology Macrophages - pathology Male Medical sciences pathology Pharmacology. Drug treatments Plaque, Atherosclerotic RNA, Messenger RNA, Messenger - analysis Rupture, Spontaneous Severity of Illness Index transcription (genetics) Transcriptome transcriptomics Vasodilator agents. Cerebral vasodilators Innate immunity Foam cell Macrophages Coronary artery disease Human pathology Human Cardiovascular disease Coronary heart disease Immunity Vascular disease Anatomic pathology Atherosclerosis Macrophage
ISSN:	0021-9150, 1879-1484, 1879-1484
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Shrnutí:	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. 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. 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. ► We assessed macrophage subsets in human plaques through transcriptomics and IHC. ► Signatures for M1 and M2 macrophage subsets persist throughout plaque progression. ► M1 and M2 macrophages display different distribution patterns in the vessel wall. ► M1 macrophages dominate plaque shoulders, a predilection site for rupture. ► Macrophage polarization state could hold substantial influence over plaque outcome.
Bibliografie:	http://dx.doi.org/10.1016/j.atherosclerosis.2012.09.013 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9150 1879-1484 1879-1484
DOI:	10.1016/j.atherosclerosis.2012.09.013