title: Age-related changes in plaque composition: a study in patients suffering from carotid artery stenosis.
abstract: OBJECTIVE
  The extent of atherosclerotic plaque burden and the incidence of atherosclerosis-related cardiovascular events accelerate with increasing age. The composition of the plaque is associated with plaque thrombosis and acute coronary occlusion. Surprisingly, however, the relation between advancing age and atherosclerotic plaque composition is still unclear. In the present study, we investigated the association between plaque characteristics and advancing age in a population of patients with haemodynamically significant carotid artery stenosis.
  
  
  METHODS
  Patients (N=383), ages 39-89 years, underwent carotid endarterectomy (CEA). Morphometric analysis was performed on the dissected atherosclerotic plaques to study the prevalence of fibrous and atheromatous plaques. Picro sirius red, haematoxylin eosin, alfa actin and CD68 stainings were performed to investigate the extent of collagen, calcification, smooth muscle cells and macrophages in carotid plaques, respectively. The presence of metalloproteinases-2 and -9 was assessed by ELISA.
  
  
  RESULTS
  With aging, a decrease in fibrous plaques and an increase in atheromatous plaques were observed. This was accompanied by an age-associated decrease in smooth muscle cell content in carotid plaques. Macrophage content slightly increased with age. In addition, total matrix metalloprotease (MMP)-2 was negatively and MMP-9 positively related with age. Differences in plaque phenotype were most prominent for the youngest age quartile compared with older age quartiles.
  
  
  CONCLUSIONS
  With increasing age, the morphology of atherosclerotic plaques from patients with carotid artery stenosis changes. Plaques become more atheromatous and contain less smooth muscle cells with increasing age. Local inflammation and MMP-9 levels slightly increased with age in plaques obtained from patients suffering from haemodynamically significant advanced atherosclerotic lesions.
authors.affiliation: Laboratory of Experimental Cardiology, UMCU, Utrecht, The Netherlands.
authors.forename: Olivia
authors.initials: O
authors.lastname: van Oostrom
authors.forename: Evelyn
authors.initials: E
authors.lastname: Velema
authors.forename: Arjan H
authors.initials: AH
authors.lastname: Schoneveld
authors.forename: Jean Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Peter
authors.initials: P
authors.lastname: de Bruin
authors.forename: Cees A
authors.initials: CA
authors.lastname: Seldenrijk
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Els
authors.initials: E
authors.lastname: Busser
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Jan H
authors.initials: JH
authors.lastname: Verheijen
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011446:Prospective Studies; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C067980:CD68 antigen, human; D000097382:CD68 Molecule