title: Levels of extra domain A containing fibronectin in human atherosclerotic plaques are associated with a stable plaque phenotype.
abstract: BACKGROUND
  Extra domain A (EDA), splice-variant of fibronectin, is a Toll-like receptor 4 (Tlr4) ligand. Recently, EDA has been demonstrated to enhance atherogenesis in mice but human data on the role of EDA in atherosclerotic disease are lacking. We hypothesized that EDA is associated with unstable plaque phenotypes and that plasma EDA could serve as biomarker for atherosclerosis.
  
  
  METHODS
  EDA levels were assessed in carotid endarterectomy specimen (206 patients) and related with plaque phenotype. In a second patient cohort, systemic EDA levels in atherosclerotic patients (73 patients) were compared to risk-factor matched controls (68 patients).
  
  
  RESULTS
  EDA plaque levels were associated with characteristics of stable plaques; more smooth muscle cells (P=0.003), more collagen (P=0.071) and less fat (P=0.023). Concomitantly, asymptomatic patients showed higher EDA values in the plaque compared to symptomatic patients (P=0.004). EDA plasma levels did not differ between atherosclerotic patients versus controls (P=0.134).
  
  
  CONCLUSIONS
  EDA plaque levels are higher in asymptomatic patients and are associated with a stable plaque phenotype. EDA is not a plasma marker for atherosclerotic disease. These results suggest that local presence of endogenous Tlr4 ligand EDA is not associated with in an unstable plaque phenotype in humans.
authors.affiliation: Experimental Cardiology Laboratory, Cardiology, University Medical Center Utrecht, The Netherlands.
authors.forename: J Karlijn
authors.initials: JK
authors.lastname: van Keulen
authors.forename: Dominique P
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Manon M Oude
authors.initials: MM
authors.lastname: Nijhuis
authors.forename: Els
authors.initials: E
authors.lastname: Busser
authors.forename: Evelyn
authors.initials: E
authors.lastname: Velema
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: de Vries
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000378:metabolism*; D015415:Biomarkers; D015331:Cohort Studies; D005353:Fibronectins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D042361:Mammary Glands, Human / Q000098:blood supply; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010641:Phenotype; D011446:Prospective Studies; D017434:Protein Structure, Tertiary; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005353:Fibronectins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D020782:Matrix Metalloproteinases