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.


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.
Papaspyridonos
Marianna
M
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
McNeill
Eileen
E
de Bono
Joe P
JP
Smith
Alberto
A
Burnand
Kevin G
KG
Channon
Keith M
KM
Greaves
David R
DR
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D015415:Biomarkers; D037502:Galectin 3; D012313:RNA