title: Expression and Localization of Granzymes and Perforin in Human Calcific Aortic Valve Disease.
abstract: OBJECTIVE
  Calcified aortic valve disease (CAVD) is an actively regulated disease that shares pathophysiological hallmarks with atherosclerosis. One of these common features is extracellular matrix (ECM) remodeling, which consists of a dynamic degradation and deposition of the ECM composition. Granzymes (Grs) are ECM- degrading and pro-apoptotic proteases that have been detected in atherosclerotic lesions, but their role in CAVD remains unknown.
  
  
  METHODS
  The expression of granzymes and perforin was characterized in heavily stenotic valves (n = 20) and control valves (n = 6) using quantitative RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Quantitative RT-PCR revealed that levels of granzymes A, B, H, K and M mRNA were 4.9-fold (p < 0.001), 7.1-fold (p < 0.001), 4.6-fold (p < 0.001), 4.7-fold (p < 0.001) and 2.8-fold (p = 0.069) higher, respectively, in stenotic aortic valves than in control valves. Perforin mRNA levels were 3.6-fold (p < 0.001) higher in stenotic valves than in control valves. Granzyme A immunohistochemical positivity was observed in mast cells and lymphocytes, granzyme H in mast cells but not in lymphocytes, and granzyme K in lymphocytes but not in mast cells. A statistical analysis was also performed to investigate the effect of statin treatment on granzyme expression, but no differences were found when compared to non-statin-treated patients.
  
  
  CONCLUSIONS
  The data acquired showed that CAVD is characterized by an increased expression of granzymes A, B, H, K, and perforin.
authors.forename: Pauli
authors.initials: P
authors.lastname: Ohukainen
authors.forename: Juha
authors.initials: J
authors.lastname: Näpäkangas
authors.forename: Pasi
authors.initials: P
authors.lastname: Ohtonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Panu
authors.initials: P
authors.lastname: Taskinen
authors.forename: Tuomas
authors.initials: T
authors.lastname: Peltonen
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002114:Calcinosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D053804:Granzymes / Q000032:analysis* / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C510468:PRF1 protein, human; D012333:RNA, Messenger; D054353:Perforin; D053804:Granzymes