This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/3/433    most recent ATVBAHA.107.159160v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Papaspyridonos, M. Articles by Greaves, D. R. Search for Related Content PubMed PubMed Citation Articles by Papaspyridonos, M. Articles by Greaves, D. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:433.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Galectin-3 Is an Amplifier of Inflammation in Atherosclerotic Plaque Progression Through Macrophage Activation And Monocyte Chemoattraction

Marianna Papaspyridonos; Eileen McNeill; Joe P. de Bono; Alberto Smith; Kevin G. Burnand; Keith M. Channon; David R. Greaves

From the Sir William Dunn School of Pathology (M.P., D.R.G.), University of Oxford; the Department of Cardiovascular Medicine (E.M., J.P.d.B., K.M.C.), University of Oxford; and the Academic Department of Surgery (A.S., K.G.B.), Cardiovascular Division, King’s College, London, UK.

Correspondence to David R Greaves, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE. E-mail david.greaves{at}path.ox.ac.uk

Abstract

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.

Galectin-3 was upregulated in advanced human and murine ApoE^–/– atherosclerotic plaques. Mediators released in response to Gal-3 treatment in macrophages increased monocyte chemotaxis, and microarray analysis confirmed the upregulation of several key chemoattractant molecules. Gal-3 is an amplifier of inflammation that could be used as a marker of atherosclerotic plaque progression or target for atherosclerosis.

Key Words: galectin-3 • chemokines • atherosclerosis • macrophages • inflammation