title: Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome.
abstract: OBJECTIVE
  Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are prevalent in the arterial wall throughout the arterial system and are associated with local plaque destabilization. We hypothesized that local MMP plaque levels are predictive for atherosclerotic cardiovascular events in other vascular territories.
  
  
  RESULTS
  Atherosclerotic plaques were obtained from 543 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid-core, smooth muscle cells, collagen, calcification, and presence of plaque haemorrhage. MMP-2, MMP-8, and MMP-9 levels were assessed within the plaque. Following CEA, all patients underwent follow-up during 3 years. The primary outcome was defined as the composite of vascular death, non-fatal vascular event, and surgical or percutaneous vascular intervention. In contrast with MMP-2 plaque levels, MMP-8 and MMP-9 levels in the plaque were associated with an unstable carotid plaque composition and clinical presentation at baseline. Increased plaque MMP-8 level (>4.58) was associated with an increased risk for the occurrence of secondary manifestations of atherosclerotic disease during follow-up [hazard ratio = 1.76, 95% CI (1.25-2.48)] (P= 0.001), whereas plaque MMP-2 and MMP-9 levels were not predictive for systemic cardiovascular events.
  
  
  CONCLUSIONS
  In contrast with MMP-2, increased carotid MMP-8 and MMP-9 plaque levels are associated with an unstable plaque phenotype. High collagenase MMP-8 levels in the carotid plaque are associated with the occurrence of systemic cardiovascular outcome during follow-up.
authors.affiliation: Experimental Cardiology Laboratory, Division heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Peeters
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Jan H
authors.initials: JH
authors.lastname: Verheijen
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Newby
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D020521:Stroke / Q000401:mortality
chemical_list: D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9