TY - JOUR
T1 - Reduced number and function of endothelial progenitor cells in patients with aortic valve stenosis
T2 - A novel concept for valvular endothelial cell repair
AU - Matsumoto, Yasuharu
AU - Adams, Volker
AU - Walther, Claudia
AU - Kleinecke, Caroline
AU - Brugger, Peter
AU - Linke, Axel
AU - Walther, Thomas
AU - Mohr, Friedrich Wilhelm
AU - Schuler, Gerhard
N1 - Funding Information:
A research grant from the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad to Y.M. In addition this study was funded by an institutional grant to V.A.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Ageing
KW - Aortic valve stenosis
KW - Apoptosis
KW - Endothelial progenitor cells
KW - Senescence
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U2 - 10.1093/eurheartj/ehn501
DO - 10.1093/eurheartj/ehn501
M3 - Article
C2 - 19010796
AN - SCOPUS:59749083468
VL - 30
SP - 346
EP - 355
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 3
ER -