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Oksala, N.K.J.* ; Seppälä, I.* ; Rahikainen, R.* ; Mäkelä, K.M.* ; Raitoharju, E.* ; Illig, T. ; Klopp, N. ; Kholova, I.* ; Laaksonen, R.* ; Karhunen, P.J.* ; Hytönen, V.P.* ; Lehtimäki, T.*

Synergistic expression of histone deacetylase 9 and matrix metalloproteinase 12 in M4 macrophages in advanced carotid plaques.

Eur. J. Vasc. Endovasc. Surg. 53, 632-640 (2017)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
OBJECTIVE/BACKGROUND: Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. METHODS: This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques (n = 68) and left internal thoracic (LITA) controls (n = 28) and plaque histological severity assessed. Correlation and hierarchical cluster analysis was utilised. RESULTS: HDAC9 was associated with MMP12 expression in carotid plaques (r = .46, p = .012) and controls (r = -.44, p = .034). HDAC9 and MMP12 clustered with inflammatory macrophage markers but not with smooth muscle cell (SMC) rich markers. In plaques from all arterial sites, MMP12 but not HDAC9 showed positive correlation (p < .05) with M2 and M4 polarized macrophage markers, and negative correlation with SMC rich signatures. In the carotid plaques, all M4 macrophage markers associated with MMP12 and HDAC9. The negative association of MMP12 with SMC rich signatures was pronounced in the carotid plaques. Neither HDAC9 nor MMP12 associated consistently with plaque stabilisation or thrombosis related genes. Immunohistochemistry further supported the association between HDAC9 and MMP12 in atherosclerotic plaques. CONCLUSION: M4 macrophages are a possible source for HDAC9 and MMP12 expression in advanced human plaques.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Advanced Carotid Plaques ; Gene Expression And Regulation ; Hdac9 ; Mmp12
ISSN (print) / ISBN 1078-5884
e-ISSN 1078-5884
Zeitschrift European Journal of Vascular and Endovascular Surgery
Quellenangaben Band: 53, Heft: 5, Seiten: 632-640 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)