title: Increased circulating concentrations and augmented myocardial extraction of osteoprotegerin in heart failure due to left ventricular pressure overload.
abstract: BACKGROUND
  Osteoprotegerin (OPG) and the receptor activator of nuclear factor-kappaB ligand (RANKL), two cytokines regulating bone remodeling, have recently been raised as potential pathogenetic factors in cardiovascular diseases. We have studied circulating and myocardial OPG and RANKL in patients having severe aortic stenosis (AS) with or without heart failure (HF).
  
  
  METHODS
  We studied 131 adults with AS. Blood was sampled from the aortic root, coronary sinus, and femoral vein at cardiac catheterization. LV myocardial biopsies were taken at surgery. Plasma OPG and soluble (s)RANKL were analyzed by ELISA, and myocardial OPG and RANKL by RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Circulating OPG was elevated in AS patients with HF, the association being independent of age, sex, and presence of coronary artery disease (beta=0.17, p=0.033). Elevated plasma OPG decreased after valve replacement in patients with preoperative HF (p=0.0005). Relative to its concentration in the aortic root, plasma OPG was reduced in the coronary sinus (p<0.05) and in the femoral vein (p<0.001), these arteriovenous gradients being accentuated in HF (p=0.003).
  
  
  CONCLUSIONS
  HF due to LV pressure overload in AS increases circulating OPG and augments OPG extraction by the heart and peripheral tissues. OPG may be involved in the pathogenesis of HF and could serve as a useful biomarker in HF due to LV pressure overload.
authors.affiliation: Wihuri Research Institute, and the Transplantation Unit, Helsinki University Centeral Hospital, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Helske
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Kaija
authors.initials: K
authors.lastname: Salmela
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
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000503:physiopathology*; D015415:Biomarkers; D016207:Cytokines; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D008297:Male; D009206:Myocardium / Q000473:pathology*; D053244:Osteoprotegerin / Q000097:blood / Q000494:pharmacology*; D010865:Pilot Projects; D053246:Receptor Activator of Nuclear Factor-kappa B; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B