title: High-density lipoproteins (HDL) are present in stenotic aortic valves and may interfere with the mechanisms of valvular calcification.
abstract: OBJECTIVE
  To determine whether differences exist in valvular high density lipoprotein (HDL) content between non-stenotic and stenotic aortic valves, and whether HDL could retard valvular calcification locally.
  
  
  METHODS
  Stenotic aortic valves were obtained from valve replacement surgery and non-stenotic control valves from cardiac transplantations or at autopsy. The valvular localization and concentration of apolipoproteinA-I (apoA-I) were analyzed by immunohistochemistry and ELISA. The effects of HDL on the secretion of calcifying mediators and proinflammatory cytokines by cultured aortic valve myofibroblasts were assessed by ELISA and real-time PCR.
  
  
  RESULTS
  The concentration of apoA-I was higher in control than in stenotic valves (p < 0.05). ApoA-I surrounded the calcific deposits in stenotic valves, co-localizing with apoB, apoE, and osteoprotegerin (OPG). Incubation of cultured valve myofibroblasts with HDL increased their secretion of OPG (p < 0.001). Furthermore, incubation of myofibroblasts with HDL led to decreased mRNA expression of tumor necrosis factor alpha (TNF-α) (p < 0.05).
  
  
  CONCLUSIONS
  The amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-α in vitro. Since OPG is known to inhibit and TNF-α to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Jaakko I
authors.initials: JI
authors.lastname: Lommi
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
authors.forename: Satu
authors.initials: S
authors.lastname: Helske
mesh_terms: D001021:Aortic Valve / Q000378:metabolism* / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001344:Autopsy; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control / Q000601:surgery; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005387:Finland; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D053244:Osteoprotegerin; D012333:RNA, Messenger; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha