Monocytes/macrophages activation contributes to b-gamma-glutamyltransferase accumulation inside atherosclerotic plaques

Journal of Translational Medicine

Research

Silvana Cianchetti¹  Maria Franzini²  Vanna Fierabracci²  Alfonso Pompella²  Alessandro Corti²  Evelina Lorenzini²  Eugenia Belcastro³  Angela Pucci⁴  Silvia Masotti⁵ 

[1] Department of Surgery and Medical, Molecular, and Critical Area Pathology, Medical School, University of Pisa, Pisa, Italy;Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy;Department of Translational Research and New Technologies in Medicine and Surgery, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy;CITHEFOR-EA 3452, Faculté de Pharmacie, Université de Lorraine, Nancy, France;Histopathology Department, University Hospital, Pisa, Italy;Life Science Institute, Scuola Superiore Sant’Anna, Pisa, Italy;

关键词: Gamma-glutamyltransferase;    b-GGT fraction;    Monocytes;    Macrophages;    Atherosclerosis;   

DOI  :  10.1186/s12967-015-0687-6

 received in 2015-08-10, accepted in 2015-10-04,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundGamma-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.MethodsGGT 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Belcastro et al. 2015