title: Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis: a novel concept for valvular endothelial cell repair.
abstract: OBJECTIVE
  Endothelial destruction and calcification primarily occur at the aortic side of the calcified aortic valves (AVs). This study investigated whether degenerative AV stenosis (AS) is associated with the presence of valvular endothelial senescence and a reduction in the number and function of endothelial progenitor cells (EPCs).
  
  
  RESULTS
  Fifteen patients with severe AS and 18 age-matched control subjects were enrolled. Senescence-associated beta-galactosidase activity was mostly localized on the valvular endothelial cells (ECs) of the explanted AVs and highly coincided with the calcified lesion at the aortic side. The number (9.3 +/- 8.3 vs. 20.5 +/- 9.0 cells per 10(6) mononuclear cells; P < 0.01) and the migratory capacity (107.8 +/- 54.6 vs. 185.0 +/- 68.8 cells per 1000 cells; P < 0.01) of EPCs evaluated by FACS analysis or migration assay were significantly reduced in AS when compared with control. As possible mechanisms of alterations in EPCs, caspase-3 activity was significantly increased, whereas telomere-repeating factor-2 expression quantified by western blot was significantly reduced in EPCs from AS when compared with control.
  
  
  CONCLUSIONS
  Reduced regenerative capacity of valvular ECs due to senescence and decreased levels of EPCs might be, at least in part, a pathological link for the destruction of valvular ECs, resulting in progression of degenerative AS.
authors.affiliation: Department of Cardiology, Heart Center Leipzig, University of Leipzig, Strümpellstrasse 39, D-04289 Leipzig, Germany.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Claudia
authors.initials: C
authors.lastname: Walther
authors.forename: Caroline
authors.initials: C
authors.lastname: Kleinecke
authors.forename: Peter
authors.initials: P
authors.lastname: Brugger
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Mohr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000097:blood; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D006328:Cardiac Catheterization; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D016922:Cellular Senescence; D018450:Disease Progression; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D053148:Caspase 3