title: High levels of S100A12 are associated with recent plaque symptomatology in patients with carotid atherosclerosis.
abstract: OBJECTIVE
  Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis.
  
  
  METHODS
  Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes.
  
  
  RESULTS
  Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1β, interferon γ, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12.
  
  
  CONCLUSIONS
  Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability.
authors.affiliation: Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. azhar.abbas@ous-hf.no
authors.forename: Azhar
authors.initials: A
authors.lastname: Abbas
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.forename: Vigdis
authors.initials: V
authors.lastname: Bjerkeli
authors.forename: Ellen B Lund
authors.initials: EB
authors.lastname: Sagen
authors.forename: Annika
authors.initials: A
authors.lastname: Michelsen
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.forename: Kirsten Krohg
authors.initials: KK
authors.lastname: Sørensen
authors.forename: Sverre
authors.initials: S
authors.lastname: Holm
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D040501:Calgranulin A / Q000097:blood; D040502:Calgranulin B / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000097:blood* / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000097:blood; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000097:blood; D018615:Ultrasonography, Doppler, Color
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D012333:RNA, Messenger; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4