Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression.

Détails

ID Serval
serval:BIB_9C611AD556F4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression.
Périodique
Blood
Auteur⸱e⸱s
Vassallo P.F., Simoncini S., Ligi I., Chateau A.L., Bachelier R., Robert S., Morere J., Fernandez S., Guillet B., Marcelli M., Tellier E., Pascal A., Simeoni U., Anfosso F., Magdinier F., Dignat-George F., Sabatier F.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
123
Numéro
13
Pages
2116-2126
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low-birth-weight subjects, especially preterm (PT) infants. We recently reported impaired angiogenic activity of endothelial colony-forming cells (ECFCs) in this condition. We hypothesized that ECFC dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared with ECFCs from term neonates (n = 18), ECFCs isolated from PT (n = 29) display an accelerated senescence sustained by growth arrest and increased senescence-associated β-galactosidase activity. Increased p16(INK4a) expression, in the absence of telomere shortening, indicates that premature PT-ECFC aging results from stress-induced senescence. SIRT1 level, a nicotinamide adenine dinucleotide-dependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFC angiogenic defect in a SIRT1-dependent manner. SIRT1 overexpression also restores PT-ECFC capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of the PT-ECFC angiogenic defect. These findings lay new grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy.
Mots-clé
Case-Control Studies, Cell Aging/physiology, Cells, Cultured, Down-Regulation/physiology, Endothelial Cells/physiology, Fetal Blood/cytology, Hematopoietic Stem Cells/physiology, Humans, Infant, Newborn, Infant, Premature/blood, Premature Birth/blood, Sirtuin 1/genetics, Stress, Physiological/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2015 12:02
Dernière modification de la notice
20/08/2019 15:03
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