Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis: A novel concept for valvular endothelial cell repair

Yasuharu Matsumoto, Volker Adams, Claudia Walther, Caroline Kleinecke, Peter Brugger, Axel Linke, Thomas Walther, Friedrich Wilhelm Mohr, Gerhard Schuler

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Aims: 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). Methods and results: Fifteen patients with severe AS and 18 age-matched control subjects were enrolled. Senescence-associated β-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 106 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)346-355
Number of pages10
JournalEuropean Heart Journal
Volume30
Issue number3
DOIs
Publication statusPublished - 2009 Feb

Keywords

  • Ageing
  • Aortic valve stenosis
  • Apoptosis
  • Endothelial progenitor cells
  • Senescence

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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