title: Matrix Gla protein regulates calcification of the aortic valve.
abstract: BACKGROUND
  The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs.
  
  
  METHODS
  Human AVICs were isolated from normal aortic valves from explanted hearts (n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients (n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2-6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann-Whitney U test (P < 0.05).
  
  
  RESULTS
  MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay.
  
  
  CONCLUSIONS
  An important anti-calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important "anti-calcification" protein may contribute to calcification of the aortic valve.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado. Electronic address: Neil.Venardos@ucdenver.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Venardos
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Daine
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Thomas Brett
authors.initials: TB
authors.lastname: Reece
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
mesh_terms: D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein
keywords: Aortic stenosis; Matrix Gla-protein; Valve interstitial cell