title: Matrix metalloproteinase 7 is associated with symptomatic lesions and adverse events in patients with carotid atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.
  
  
  METHODS
  Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50-69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.
  
  
  RESULTS
  Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.
  
  
  CONCLUSIONS
  Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.
authors.affiliation: Department of Neurology, University of Oslo, Oslo, Norway ; Research Institute of Internal Medicine, University of Oslo, Oslo, Norway.
authors.forename: Azhar
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Neurology, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Oslo, Oslo, Norway.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.affiliation: Department of Neurology, Østfold Hospital Trust, Fredrikstad, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Almås
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Østfold Hospital Trust, Fredrikstad, Norway.
authors.forename: Dorte
authors.initials: D
authors.lastname: Bundgaard
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Vigdis
authors.initials: V
authors.lastname: Bjerkeli
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ellen Lund
authors.initials: EL
authors.lastname: Sagen
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Holm
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Neurology, University of Oslo, Oslo, Norway ; Research Institute of Internal Medicine, University of Oslo, Oslo, Norway.
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.affiliation: Research Institute of Internal Medicine, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
mesh_terms: D000368:Aged; D002340:Carotid Artery Diseases / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors
chemical_list: D020783:Matrix Metalloproteinase 7