title: Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability.
abstract: OBJECTIVE
  Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.
  
  
  METHODS
  Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque.
  
  
  RESULTS
  Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01), OPG (10.2% of ROI vs 3.4% of ROI, p<0.05) and pericytes (19% of ROI vs 3.8% of ROI, p<0.05) were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p = 0.05). In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG.
  
  
  CONCLUSIONS
  OPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Davaine
authors.affiliation: INSERM, UMR 957, Nantes, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Quillard
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Brion
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lapérine
authors.affiliation: Centre Hospitalier Universitaire, Nantes, France; Institut du Thorax, Nantes, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Guyomarch
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Merlini
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Chatelais
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Guilbaud
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France.
authors.forename: Meadhbh Áine
authors.initials: MÁ
authors.lastname: Brennan
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Charrier
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: Centre Hospitalier Universitaire, Nantes, France; Institut du Thorax, Nantes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Gouëffic
authors.affiliation: INSERM, UMR 957, Nantes, France; Université de Nantes, Nantes atlantique universités, Nantes, France; Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Heymann
mesh_terms: D051929:CD146 Antigen / Q000378:metabolism; D016893:Carotid Stenosis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D006801:Humans; D008679:Metaplasia; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology*; D053245:RANK Ligand / Q000378:metabolism; D061205:Vascular Calcification
chemical_list: D051929:CD146 Antigen; D053244:Osteoprotegerin; D053245:RANK Ligand