title: Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease.
abstract: BACKGROUND
  Calcific aortic valve disease (CAVD) is the most common cause of acquired valve disease. Initial phases of CAVD include thickening of the cusps, whereas advanced stages are associated with biomineralization and reduction of the aortic valve area. These conditions are known as aortic valve sclerosis (AVSc) and aortic valve stenosis (AVS), respectively. Because of its asymptomatic presentation, little is known about the molecular determinants of AVSc. The aim of this study was to correlate plasma and tissue osteopontin (OPN) levels with echocardiographic evaluation for the identification of asymptomatic patients at risk for CAVD. In addition, our aim was to analyze the differential expression and biological function of OPN splicing variants as biomarkers of early and late stages of CAVD.
  
  
  METHODS
  From January 2010 to February 2011, 310 patients were enrolled in the study. Patients were divided into 3 groups based on transesophageal echocardiographic (TEE) evaluation: controls (56 patients), AVSc (90 patients), and AVS (164 patients). Plasma and tissue OPN levels were measured by immunohistochemical evaluation, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (qPCR).
  
  
  RESULTS
  Patients with AVSc and AVS have higher OPN levels compared with controls. OPN levels are elevated in asymptomatic patients with AVSc with no appearance of calcification during TEE evaluation. OPN splicing variants OPN-a, OPN-b, and OPN-c are differentially expressed during CAVD progression and are able to inhibit biomineralization in a cell-based biomineralization assay.
  
  
  CONCLUSIONS
  The analysis of the differential expression of OPN splicing variants during CAVD may help in developing diagnostic and risk stratification tools to follow the progression of asymptomatic aortic valve degeneration.
authors.affiliation: Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Juan B
authors.initials: JB
authors.lastname: Grau
authors.forename: Paolo
authors.initials: P
authors.lastname: Poggio
authors.forename: Rachana
authors.initials: R
authors.lastname: Sainger
authors.forename: William J
authors.initials: WJ
authors.lastname: Vernick
authors.forename: William F
authors.initials: WF
authors.lastname: Seefried
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Field
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.forename: Michael A
authors.initials: MA
authors.lastname: Acker
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
mesh_terms: D000368:Aged; D001021:Aortic Valve; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D018450:Disease Progression; D017548:Echocardiography, Transesophageal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006349:Heart Valve Diseases / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D053495:Osteopontin; D012313:RNA
references.citation: J Heart Valve Dis. 1996 Jan;5(1):50-7
references.pmid: 8834726
references.citation: Age Ageing. 2004 Nov;33(6):538-44
references.pmid: 15308457
references.citation: J Heart Valve Dis. 2010 Jul;19(4):441-52
references.pmid: 20845891
references.citation: Arch Intern Med. 2002 Nov 11;162(20):2345-7
references.pmid: 12418948
references.citation: Circ Res. 1999 Feb 5;84(2):166-78
references.pmid: 9933248
references.citation: C R Acad Sci III. 1997 Jan;320(1):49-57
references.pmid: 9099263
references.citation: Circulation. 2009 May 26;119(20):2653-5
references.pmid: 19470899
references.citation: Ann Thorac Surg. 2001 May;71(5 Suppl):S406-7
references.pmid: 11388235
references.citation: J Am Coll Cardiol. 2007 Sep 25;50(13):1205-13
references.pmid: 17888836
references.citation: J Cell Physiol. 2011 Aug;226(8):2139-49
references.pmid: 21520066
references.citation: J Heart Valve Dis. 2007 Jul;16(4):362-9
references.pmid: 17702360
references.citation: Am J Med. 2011 Feb;124(2):103-10
references.pmid: 21295189
references.citation: Arq Bras Cardiol. 2009 Sep;93(3):299-306
references.pmid: 19851659
references.citation: Curr Treat Options Cardiovasc Med. 2005 Dec;7(6):437-42
references.pmid: 16283970
references.citation: J Thorac Cardiovasc Surg. 2009 Jul;138(1):196-9
references.pmid: 19577079
references.citation: N Engl J Med. 2000 Aug 31;343(9):611-7
references.pmid: 10965007
references.citation: Eur J Cardiothorac Surg. 2009 Mar;35(3):493-504
references.pmid: 19162497
references.citation: Heart. 2004 Jan;90(1):77-81
references.pmid: 14676250
references.citation: Circulation. 2005 Jun 21;111(24):3316-26
references.pmid: 15967862