title: Carotid atherosclerotic plaque matrix metalloproteinase-12-positive macrophage subpopulation predicts adverse outcome after endarterectomy.
abstract: BACKGROUND
  Matrix metalloproteinase-12 (MMP-12) promotes atherosclerosis in animal models. MMP-12 is expressed in only a subset of foam-cell macrophages (FCMs) in human plaques. We investigated whether the prevalence of this MMP-12-expressing subpopulation is a prognostic indicator of adverse outcome in patients after carotid endarterectomy (CEA).
  
  
  RESULTS
  Serial sections of culprit lesions from 236 patients who underwent CEA and had undergone 3 years of clinical follow-up were stained immunocytochemically for MMP-12 and for CD68, and the MMP-12/CD68 ratio was used to quantify the MMP-12-expressing subpopulation. A high MMP-12/CD68 ratio correlated with a high content of lipid and total macrophages and a low content of vascular smooth muscle cells, as well as with MMP-8 (R=0.211, P=0.001), MMP-9 (R=0.251, P<0.001), and cleaved caspase-3 (R=0.142, P=0.036) activity measured in a neighboring segment. Dual immunohistochemical examination confirmed the location of MMP-12 in a subpopulation of MMP-8- and MMP-9-positive FCMs, whereas all apoptotic FCMs were MMP-12 positive. Patients who yielded plaques within the highest quartile compared with the lowest quartile of MMP-12/CD68 ratio had a 2.4-fold (hazard ratio, 2.4; 95% CI, 1.1- to 5.1-fold; adjusted P=0.027) increased risk of major adverse cardiovascular event and a 3.4-fold (3.4; 1.2- to 9.6-fold, P=0.024) increased risk for stroke.
  
  
  CONCLUSIONS
  The prevalence of an MMP-12-positive subset of FCMs is a prognostic marker for adverse clinical outcome after CEA.
authors: Laboratory Experimental Cardiology, UMC Utrecht, Utrecht, the Netherlands.
authors: Vincent P W
authors: VP
authors: Scholtes
authors: Jason L
authors: JL
authors: Johnson
authors: Nicholas
authors: N
authors: Jenkins
authors: Graciela B
authors: GB
authors: Sala-Newby
authors: Jean-Paul P M
authors: JP
authors: de Vries
authors: Gert Jan
authors: GJ
authors: de Borst
authors: Dominique P V
authors: DP
authors: de Kleijn
authors: Frans L
authors: FL
authors: Moll
authors: Gerard
authors: G
authors: Pasterkamp
authors: Andrew C
authors: AC
authors: Newby
mesh_terms: D000368:Aged; D016894:Endarterectomy, Carotid; D005260:Female; D005487:Foam Cells / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D009203:Myocardial Infarction / Q000453:epidemiology; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D011184:Postoperative Period; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology
chemical_list: D053508:Matrix Metalloproteinase 12
keywords: MMP-12; atherosclerosis; macrophages; outcome