title: Monocytes/macrophages activation contributes to b-gamma-glutamyltransferase accumulation inside atherosclerotic plaques.
abstract: BACKGROUND
  Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque.
  
  
  METHODS
  GGT expression and release were studied in human monocytes isolated from peripheral blood of healthy donors. The growth factors GM-CSF and M-CSF were used to induce differentiation into M1-like and M2-like macrophages, respectively. Plaque GGT was investigated in tissue samples obtained from patients undergoing carotid endoarterectomy.
  
  
  RESULTS
  We found that M1-like macrophages express higher levels of GGT as compared to M2-like, and that both monocytes and M1-like macrophages-but not M2-like-are able to release the b-GGT fraction upon activation with pro-inflammatory stimuli. Western blot analysis of b-GGT extracted from plaques confirmed the presence of a GGT immunoreactive peptide coincident with that of macrophages.
  
  
  CONCLUSIONS
  Our data indicate that macrophages characterized by a pro-inflammatory phenotype may contribute to intra-plaque accumulation of b-GGT, which in turn may play a role in the progression of atherosclerosis by modulating inflammatory processes and favouring plaque instability.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. eugenia.belcastro@virgilio.it.|CITHEFOR-EA 3452, Faculté de Pharmacie, Université de Lorraine, Nancy, France. eugenia.belcastro@virgilio.it.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Belcastro
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. maria.franzini@unipi.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Franzini
authors.affiliation: Department of Surgery and Medical, Molecular, and Critical Area Pathology, Medical School, University of Pisa, Pisa, Italy. silvana.cianchetti@dctv.unipi.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Cianchetti
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. evelina.lorenzini@dps.unipi.it.
authors.forename: Evelina
authors.initials: E
authors.lastname: Lorenzini
authors.affiliation: Life Science Institute, Scuola Superiore Sant'Anna, Pisa, Italy. silvi87@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Masotti
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. vanna.fierabracci@med.unipi.it.
authors.forename: Vanna
authors.initials: V
authors.lastname: Fierabracci
authors.affiliation: Histopathology Department, University Hospital, Pisa, Italy. a.pucci@ao-pisa.toscana.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. alfonso.pompella@med.unipi.it.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pompella
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. alessandro.corti@med.unipi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corti
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D002850:Chromatography, Gel; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008833:Microcirculation; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000201:enzymology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005723:gamma-Glutamyltransferase