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 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.