Distribution of macrophage polarization markers in human atherosclerosis

• Published in: Atherosclerosis Vol. 225; no. 2; pp. 461 - 468
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.12.2012; Elsevier
• Subjects: Adventitia - immunology; Adventitia - pathology; Aged; Aged, 80 and over; atherogenesis; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - analysis; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Cardiovascular system; Carotid Arteries - immunology; Carotid Arteries - pathology; Carotid Artery Diseases - genetics; Carotid Artery Diseases - immunology; Carotid Artery Diseases - pathology; Coronary artery disease; Disease Progression; Female; Fibrosis; Foam cell; Gene Expression Profiling; Gene Expression Regulation; hemorrhage; Human pathology; Humans; Immunohistochemistry; Inflammation Mediators - analysis; Innate immunity; Macrophages; Macrophages - classification; Macrophages - immunology; Macrophages - pathology; Male; Medical sciences; Pharmacology. Drug treatments; Plaque, Atherosclerotic; 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
• DOI: 10.1016/j.atherosclerosis.2012.09.013

Abstract 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. Methods & 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. Conclusion 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.