Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction.
OBJECTIVE: Galectin-3 (Gal-3) is a 26-kDa lectin known to regulate many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to atherosclerotic plaque progression by enhancing monocyte chemoattraction through macrophage activation. METHODS AND...
| Autores principales: | , , , , , , |
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| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
2008
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| _version_ | 1826270311753973760 |
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| author | Papaspyridonos, M McNeill, E de Bono, J Smith, A Burnand, K Channon, K Greaves, D |
| author_facet | Papaspyridonos, M McNeill, E de Bono, J Smith, A Burnand, K Channon, K Greaves, D |
| author_sort | Papaspyridonos, M |
| collection | OXFORD |
| description | OBJECTIVE: Galectin-3 (Gal-3) is a 26-kDa lectin known to regulate many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to atherosclerotic plaque progression by enhancing monocyte chemoattraction through macrophage activation. METHODS AND RESULTS: Gal-3 was found to be upregulated in unstable plaque regions of carotid endarterectomy (CEA) specimens compared with stable regions from the same patient (3.2-fold, P<0.05) at the mRNA (n=12) and (2.3-fold, P<0.01) at the protein level (n=9). Analysis of aortic tissue from ApoE-/- mice on a high fat diet (n=14) and wild-type controls (n=9) showed that Gal-3 mRNA and protein levels are elevated by 16.3-fold (P<0.001) and 12.2-fold (P<0.01) and that Gal-3 staining colocalizes with macrophages. In vitro, conditioned media from Gal-3-treated human macrophages induced an up to 6-fold increase in human monocyte chemotaxis (P<0.01, ANOVA), an effect that was reduced by 66 and 60% by Pertussis Toxin (PTX) and the Vaccinia virus protein 35K, respectively. Microarray analysis of human macrophages and subsequent qPCR validation confirmed the upregulation of CC chemokines in response to Gal-3 treatment. CONCLUSIONS: Our data suggest that Gal-3 is both a marker of atherosclerotic plaque progression and a central contributor to the pathology by amplification of key proinflammatory molecules. |
| first_indexed | 2024-03-06T21:38:52Z |
| format | Journal article |
| id | oxford-uuid:473529e7-a98c-474f-a1aa-b87e6c273cd1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:38:52Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:473529e7-a98c-474f-a1aa-b87e6c273cd12022-03-26T15:18:42ZGalectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:473529e7-a98c-474f-a1aa-b87e6c273cd1EnglishSymplectic Elements at Oxford2008Papaspyridonos, MMcNeill, Ede Bono, JSmith, ABurnand, KChannon, KGreaves, D OBJECTIVE: Galectin-3 (Gal-3) is a 26-kDa lectin known to regulate many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to atherosclerotic plaque progression by enhancing monocyte chemoattraction through macrophage activation. METHODS AND RESULTS: Gal-3 was found to be upregulated in unstable plaque regions of carotid endarterectomy (CEA) specimens compared with stable regions from the same patient (3.2-fold, P<0.05) at the mRNA (n=12) and (2.3-fold, P<0.01) at the protein level (n=9). Analysis of aortic tissue from ApoE-/- mice on a high fat diet (n=14) and wild-type controls (n=9) showed that Gal-3 mRNA and protein levels are elevated by 16.3-fold (P<0.001) and 12.2-fold (P<0.01) and that Gal-3 staining colocalizes with macrophages. In vitro, conditioned media from Gal-3-treated human macrophages induced an up to 6-fold increase in human monocyte chemotaxis (P<0.01, ANOVA), an effect that was reduced by 66 and 60% by Pertussis Toxin (PTX) and the Vaccinia virus protein 35K, respectively. Microarray analysis of human macrophages and subsequent qPCR validation confirmed the upregulation of CC chemokines in response to Gal-3 treatment. CONCLUSIONS: Our data suggest that Gal-3 is both a marker of atherosclerotic plaque progression and a central contributor to the pathology by amplification of key proinflammatory molecules. |
| spellingShingle | Papaspyridonos, M McNeill, E de Bono, J Smith, A Burnand, K Channon, K Greaves, D Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title | Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title_full | Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title_fullStr | Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title_full_unstemmed | Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title_short | Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. |
| title_sort | galectin 3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction |
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