title: Dephosphorylation of circulating human osteopontin correlates with severe valvular calcification in patients with calcific aortic valve disease.
abstract: BACKGROUND
  Calcific Aortic Valve Disease (CAVD) is an active pathological process leading to biomineralization of the aortic cusps. We characterized circulating and tissue Osteopontin (OPN) as a biomarker for CAVD.
  
  
  OBJECTIVE
  Here we investigate the post-translational modifications of circulating OPN and correlate the phosphorylation status with the ability to prevent calcification.
  
  
  METHODS
  Circulating OPN levels were estimated in CAVD patients (n = 51) and controls (n = 56). In a subgroup of 27 subjects, OPN was purified and the phosphorylation status analyzed.
  
  
  RESULTS
  Plasma OPN levels were significantly elevated in CAVD patients as compared to the controls and correlates with the aortic valve calcium score. Our study demonstrates that phospho-threonine levels of OPN purified from controls were higher when compared to CAVD subjects, whereas phospho-serine and phospho-tyrosine levels were comparable between the two groups.
  
  
  CONCLUSIONS
  The dephosphorylation of circulating OPN correlates with severe valvular calcification in patients with CAVD.
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Department of Surgery, Division of Cardiovascular Surgery, Philadelphia, PA, USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Sainger
authors.forename: Juan B
authors.initials: JB
authors.lastname: Grau
authors.forename: Paolo
authors.initials: P
authors.lastname: Poggio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D002114:Calcinosis; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000097:blood*; D010766:Phosphorylation; D010769:Phosphothreonine / Q000097:blood; D011499:Protein Processing, Post-Translational; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D053495:Osteopontin; D010769:Phosphothreonine; D002118:Calcium