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

Details

Serval ID
serval:BIB_9C611AD556F4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression.
Journal
Blood
Author(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
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
123
Number
13
Pages
2116-2126
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
22/02/2015 12:02
Last modification date
20/08/2019 15:03
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