title: Progression of human aortic valve stenosis is associated with tenascin-C expression.
abstract: OBJECTIVE
  We sought to assess tenascin-C (TN-C) expression and its possible pathobiological impact in human aortic valve stenosis.
  
  
  BACKGROUND
  Tenascin-C, a large extracellular matrix glycoprotein, has lately been increasingly connected to cardiovascular pathologies. As TN-C is a multifunctional protein implicated in cell proliferation, migration and differentiation, we investigated the pattern of its expression in diseased human aortic valves.
  
  
  METHODS
  Fifty-five tricuspid, non-rheumatic stenotic aortic valves were collected from patients undergoing aortic valve replacement, and the controls consisted of four normal valves from individuals who had suffered traumatic death and one from a patient operated on because of a noncalcified purely regurgitant valve. A monoclonal mouse antibody to human TN-C (143DB7) was used as the primary antibody in immunostaining. To study the source of TN-C messenger RNA synthesis, some tissue samples were also examined using in situ hybridization. In order to identify smooth muscle cell differentiation, commercially available antibodies against alpha-smooth muscle actin were used, and immunophenotypic analysis of inflammatory cells was carried out by using the monoclonal mouse antibodies UCHL-1, L26 and PGM-1.
  
  
  RESULTS
  In normal valves, TN-C expression was associated with the basement membrane beneath the endothelial cells, whereas stenotic valves showed no such expression but rather immunoreactivity in the deeper layers of the valves. This reactivity was associated with the characteristics typical of the stenosing process and the increased mechanical loading caused by hypertension.
  
  
  CONCLUSIONS
  We hypothesize that the overexpression of TN-C in stenotic human aortic valves may emphasize that this disease is an active rather than a degenerative process.
authors.affiliation: Department of Surgery, University of Oulu and Oulu University Hospital, Oulu, Finland. jari.satta@oulu.fi
authors.forename: Jari
authors.initials: J
authors.lastname: Satta
authors.forename: Jukka
authors.initials: J
authors.lastname: Melkko
authors.forename: Raimo
authors.initials: R
authors.lastname: Pöllänen
authors.forename: Juha
authors.initials: J
authors.lastname: Tuukkanen
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.forename: Pasi
authors.initials: P
authors.lastname: Ohtonen
authors.forename: Ari
authors.initials: A
authors.lastname: Mennander
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D019063:Tenascin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019063:Tenascin