Abstract | BACKGROUND AND AIMS: METHODS: Plasma levels of legumain from patients with carotid stenosis (n = 254), healthy controls (n = 91), and secreted from monocyte-derived macrophages were assessed by enzyme-linked- immunosorbent assay. Quantitative PCR and immunoblotting of legumain were performed on isolated plaques and legumain localization was visualized by immunohistochemistry and fluorescence microscopy. Monocyte-derived macrophages polarized to M1 or M2 macrophages were treated with VLDL, oxLDL or cholesterol crystals (CC) and the level of legumain analysed. RESULTS: Patients with carotid stenosis had significantly higher levels of plasma legumain compared with healthy controls (median 2.0 versus 1.5 ng/ml, respectively; p = 0.003), although there was no correlation between the level of legumain and the degree of stenosis, and legumain was not an independent factor to identify patients with carotid plaques. Moreover, patients with symptoms the last 2 months had higher expressions of mature legumain, cystatin C and E/M, and the macrophage markers CD80 (M1) and CD163 (M2). Legumain co-localized with both M1 and M2 macrophages within plaques, whereas legumain mRNA expression was significantly higher (p < 0.0001) in plaques compared to non-atherosclerotic arteries (controls). Furthermore, in vitro studies showed significantly increased secretion of legumain from pro-inflammatory M1 compared to pro-resolving M2 macrophages (p = 0.014), and particularly in M1 treated with CC. In plaques, legumain was localized to structures resembling foam cells. CONCLUSIONS:
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Authors | Ngoc Nguyen Lunde, Sverre Holm, Tuva B Dahl, Inass Elyouncha, Bjørnar Sporsheim, Ida Gregersen, Azhar Abbas, Mona Skjelland, Terje Espevik, Rigmor Solberg, Harald Thidemann Johansen, Bente Halvorsen |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 257
Pg. 216-223
(02 2017)
ISSN: 1879-1484 [Electronic] Ireland |
PMID | 27940038
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Biomarkers
- Lipoproteins, LDL
- Lipoproteins, VLDL
- oxidized low density lipoprotein
- Cholesterol
- Cysteine Endopeptidases
- asparaginylendopeptidase
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Topics |
- Aged
- Biomarkers
(blood)
- Carotid Arteries
(diagnostic imaging, enzymology)
- Carotid Stenosis
(blood, diagnostic imaging, enzymology)
- Case-Control Studies
- Cell Plasticity
- Cells, Cultured
- Cholesterol
(metabolism)
- Crystallization
- Cysteine Endopeptidases
(blood)
- Female
- Foam Cells
(enzymology)
- Humans
- Lipoproteins, LDL
(metabolism)
- Lipoproteins, VLDL
(metabolism)
- Macrophage Activation
- Macrophages
(enzymology, pathology)
- Male
- Middle Aged
- Phenotype
- Plaque, Atherosclerotic
- Up-Regulation
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