title: The collagen cross-linking enzyme lysyl oxidase is associated with the healing of human atherosclerotic lesions.
abstract: BACKGROUND
  Acute clinical complications of atherosclerosis such as myocardial infarction (MI) and ischaemic stroke are usually caused by thrombus formation on the ruptured plaque surface. Collagen, the main structural protein of the fibrous cap, provides mechanical strength to the atherosclerotic plaque. The integrity of the fibrous cap depends on collagen fibre cross-linking, a process controlled by the enzyme lysyl oxidase (LOX).
  
  
  RESULTS
  We studied atherosclerotic plaques from human carotid endarterectomies. LOX was strongly expressed in atherosclerotic lesions and detected in the regions with ongoing fibrogenesis. Higher LOX levels were associated with a more stable phenotype of the plaque. In the studied population, LOX mRNA levels in carotid plaques predicted the risk for future MI. Within the lesion, LOX mRNA levels correlated positively with levels of osteoprotegerin (OPG) and negatively with markers of immune activation. The amount of LOX-mediated collagen cross-links in plaques correlated positively also with serum levels of OPG.
  
  
  CONCLUSIONS
  Lysyl oxidase may contribute to the healing of atherosclerotic lesions and to the prevention of its lethal complications. Mediators of inflammation may control LOX expression in plaques and hence plaque stability.
authors.affiliation: Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Ovchinnikova
authors.forename: L
authors.initials: L
authors.lastname: Folkersen
authors.forename: J
authors.initials: J
authors.lastname: Persson
authors.forename: J H N
authors.initials: JH
authors.lastname: Lindeman
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: N
authors.initials: N
authors.lastname: Gavrisheva
authors.forename: E
authors.initials: E
authors.lastname: Shlyakhto
authors.forename: G
authors.initials: G
authors.lastname: Paulsson-Berne
authors.forename: U
authors.initials: U
authors.lastname: Hedin
authors.forename: P S
authors.initials: PS
authors.lastname: Olofsson
authors.forename: G K
authors.initials: GK
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000201:enzymology*; D002340:Carotid Artery Diseases / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D053244:Osteoprotegerin / Q000097:blood / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000201:enzymology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors
chemical_list: D053244:Osteoprotegerin; D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase
keywords: atherosclerotic plaque; collagen; lysyl oxidase