• English
    • Welsh
  • English 
    • English
    • Welsh
  • Login
Search DSpace:
  • Home
  • Research at Cardiff Met
  • Library Services
  • Contact Us
View item 
  • DSpace home
  • Cardiff School of Sport and Health Sciences
  • Cardiovascular Health and Ageing
  • View item
  • DSpace home
  • Cardiff School of Sport and Health Sciences
  • Cardiovascular Health and Ageing
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence

Thumbnail
Author
Cardus, Anna
Uryga, Anna
Walters, Gareth
Erusalimsky, Jorge
Date
2013
Type
Article
Publisher
Oxford University Press
ISSN
0008-6363
Metadata
Show full item record
Abstract
AIMS: Although endothelial cell senescence is known to play an important role in the development of cardiovascular pathologies, mechanisms that attenuate this process have not been extensively investigated. The aim of this study was to investigate whether SIRT6, a member of the sirtuin family of NAD+-dependent protein deacetylases/ADP-ribosyltransferases, protects endothelial cells from premature senescence and dysfunction, and if so which is its mode of action. METHODS: and results mRNA expression analysis demonstrated comparable levels of SIRT1 and SIRT6 transcripts in endothelial cells derived from different vascular beds and significantly higher levels of SIRT6 in these cells relative to those in haematopoietic progenitor cells. SIRT6 depletion by RNA interference in human umbilical vein endothelial cells (HUVEC) and aortic endothelial cells reduced cell proliferation, increased the fraction of senescence-associated-β-galactosidase-positive cells, and diminished the ability of the cells to form tubule networks on Matrigel. Further examination of SIRT6-depleted HUVEC demonstrated higher intercellular-adhesion molecule-1 (ICAM-1) and plasminogen-activator inhibitor-1 mRNA, lower levels of endothelial nitric oxide synthase mRNA and protein, higher ICAM-1 surface expression, and up-regulation of p21. Fluorescence microscopy of SIRT6-depleted HUVEC stained with anti-phospho-histone H2A.X and anti-telomere-repeat-binding-factor-1 antibodies showed evidence of increased nuclear DNA damage and the formation of telomere dysfunction-induced foci. CONCLUSION: This work demonstrates that the presence of SIRT6 in endothelial cells confers protection from telomere and genomic DNA damage, thus preventing a decrease in replicative capacity and the onset of premature senescence. These findings suggest that SIRT6 may be important to maintain endothelial homeostatic functions and delay vascular ageing.
Journal/conference proceeding
Cardiovascular Research
Citation
Cardus, A., Uryga, A.K., Walters, G. and Erusalimsky, J.D. (2013) 'SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence', Cardiovascular Research, 97(3), pp.571-579.
URI
http://hdl.handle.net/10369/5254
DOI
http://dx.doi.org/10.1093/cvr/cvs352
Description
This article was published in Cardiovascular Research on 01 December 2012 (online), available at http://dx.doi.org/10.1093/cvr/cvs352
Collections
  • Cardiovascular Health and Ageing [145]

Related items

Showing items related by title, author, subject and abstract.

  • Thumbnail

    Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells 

    Kurz, D. J.; Decary, S.; Hong, Y.; Trivier, E.; Akhmedov, A.; Erusalimsky, Jorge (The Company of Biologists, 2004)
    Replicative senescence and oxidative stress have been implicated in ageing, endothelial dysfunction and atherosclerosis. Replicative senescence is determined primarily by telomere integrity. In endothelial cells the ...
  • Thumbnail

    The angiotensin-(1-7)/Mas receptor a xis protects from endothelial cell senescence via klotho and Nrf2 activation 

    Romero, Alejandra; Hipólito-Luengo, Álvaro San; Villalobos, Laura; Vallejo, Susana; Valencia, Inés; Michalska, Patrycja; Pajuelo-Lozano, Natalia; Sánchez-Pérez, Isabel; León, Rafael; Bartha, José Luis; Sanz, María J.; Erusalimsky, Jorge; Sánchez-Ferrer, Carlos F.; Romacho, Tania; Peiró, Concepción (Wiley, 2019-02-17)
    Endothelial cell senescence is a hallmark of va scular aging that pre disposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin ...
  • Thumbnail

    Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries 

    Fenton, M.; Barker, S.; Kurz, D. J.; Erusalimsky, Jorge (American Heart Association, 2001)
    The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence ...

Browse

DSpace at Cardiff MetCommunities & CollectionsBy issue dateAuthorsTitlesSubjectsThis collectionBy issue dateAuthorsTitlesSubjects

My Account

Login

Statistics

Most Popular ItemsStatistics by CountryMost Popular Authors

DSpace software copyright © 2002-2015  DuraSpace
Contact us | Send feedback | Administrator