title: Increased expression of elastolytic cathepsins S, K, and V and their inhibitor cystatin C in stenotic aortic valves.
abstract: OBJECTIVE
  To investigate the possible role of elastolytic cathepsins S, K, and V and their endogenous inhibitor cystatin C in adverse extracellular matrix remodeling of stenotic aortic valves.
  
  
  RESULTS
  Stenotic aortic valves were collected at valve replacement surgery and control valves at cardiac transplantations. The expression of cathepsins S, K, and V and cystatin C was studied by conventional and real-time polymerase chain reaction and by immunohistochemistry. Total cathepsin activity in the aortic valves was quantified by a fluorometric microassay. When compared with control valves, stenotic valves showed increased mRNA expression of cathepsins S, K, and V (P<0.05 for each) and a higher total cathepsin activity (P<0.001). In stenotic valves, cystatin C mRNA was increased (P<0.05), and cystatin C protein was found particularly in areas with infiltrates of inflammatory cells. Both cathepsin S and cystatin C were present in bony areas of the valves, whereas cathepsin V localized to endothelial cells in areas rich of neovascularization. Incubation of thin sections of aortic valves with cathepsins S, K, and V resulted in severe disruption of elastin fibers, and this cathepsin effect could be blocked by adding cystatin C to the incubation system.
  
  
  CONCLUSIONS
  Stenotic aortic valves show increased expression and activity of elastolytic cathepsins S, K, and V. These cathepsins may accelerate the destruction of aortic valvular extracellular matrix, so promoting the progression of aortic stenosis.
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Helske
authors.forename: Suvi
authors.initials: S
authors.lastname: Syväranta
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Jani
authors.initials: J
authors.lastname: Lappalainen
authors.forename: Katariina
authors.initials: K
authors.lastname: Oörni
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.forename: Jyri
authors.initials: J
authors.lastname: Lommi
authors.forename: Heikki
authors.initials: H
authors.lastname: Turto
authors.forename: Kalervo
authors.initials: K
authors.lastname: Werkkala
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D001021:Aortic Valve / Q000378:metabolism*; D001024:Aortic Valve Stenosis / Q000378:metabolism*; D016022:Case-Control Studies; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism; D005470:Fluorometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D012333:RNA, Messenger; D004549:Elastin; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K; C117627:CTSV protein, human