PMID- 20399802
OWN - NLM
STAT- MEDLINE
DCOM- 20100818
LR  - 20211028
IS  - 1872-6216 (Electronic)
IS  - 0047-6374 (Print)
IS  - 0047-6374 (Linking)
VI  - 131
IP  - 5
DP  - 2010 May
TI  - Endogenous oxidative stress prevents telomerase-dependent immortalization of 
      human endothelial cells.
PG  - 354-63
LID - 10.1016/j.mad.2010.04.004 [doi]
AB  - INTRODUCTION: With aging, oxidative stress accelerates vascular endothelial cell 
      (EC) telomere shortening-induced senescence, and may promote atherosclerosis in 
      humans. Our aim was to investigate whether an antioxidant treatment combined with 
      telomerase (hTERT) over-expression would prevent senescence of EC isolated from 
      patients with severe atherosclerosis. METHODS: Cells were isolated from internal 
      mammary arteries (n=11 donors), cultured until senescence with or without 
      N-acetylcystein (NAC) and infected, or not, with a lentivirus over-expressing 
      hTERT. RESULTS: Compared to control EC, hTERT-NAC cells had increased telomerase 
      activity, longer telomeres and underwent more cell divisions. According to the 
      donor, hTERT-NAC either delayed (n=5) or prevented (n=4) EC senescence, the 
      latter leading to cell immortalization. Lack of cell immortalization by hTERT-NAC 
      was accompanied by an absence of beneficial effect of NAC alone in paired EC. 
      Accordingly, lack of EC immortalization by hTERT-NAC was associated with high 
      endogenous susceptibility to oxidation. In EC where hTERT-NAC did not immortalize 
      EC, p53, p21 and p16 expression increased with senescence, while 
      oxidative-dependent DNA damage associated with senescence was not prevented. 
      CONCLUSION: Our data suggest that irreversible oxidative stress-dependent damages 
      associated with cardiovascular risk factors are responsible for senescence of EC 
      from atherosclerotic patients.
CI  - Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Voghel, Guillaume
AU  - Voghel G
AD  - Department of Surgery, Research Center, Montreal Heart Institute, Universite de 
      Montreal, Montreal, Quebec, Canada.
FAU - Thorin-Trescases, Nathalie
AU  - Thorin-Trescases N
FAU - Mamarbachi, Aida M
AU  - Mamarbachi AM
FAU - Villeneuve, Louis
AU  - Villeneuve L
FAU - Mallette, Frederick A
AU  - Mallette FA
FAU - Ferbeyre, Gerardo
AU  - Ferbeyre G
FAU - Farhat, Nada
AU  - Farhat N
FAU - Perrault, Louis P
AU  - Perrault LP
FAU - Carrier, Michel
AU  - Carrier M
FAU - Thorin, Eric
AU  - Thorin E
LA  - eng
GR  - 14496-4/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100424
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.7.49 (Telomerase)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
EIN - Mech Ageing Dev. 2010 Sep;131(9):599
MH  - Acetylcysteine/pharmacology
MH  - Aged
MH  - Atherosclerosis/enzymology/*physiopathology
MH  - Cells, Cultured
MH  - *Cellular Senescence
MH  - Cyclin-Dependent Kinase Inhibitor p16/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - DNA Damage
MH  - Endothelial Cells/drug effects/*enzymology
MH  - Female
MH  - Free Radical Scavengers/pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Oxidative Stress
MH  - Risk
MH  - Telomerase/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC3700881
MID - CAMS3017
OID - NLM: CAMS3017
COIS- Conflict of interest None declared.
EDAT- 2010/04/20 06:00
MHDA- 2010/08/19 06:00
PMCR- 2013/07/03
CRDT- 2010/04/20 06:00
PHST- 2010/01/04 00:00 [received]
PHST- 2010/02/26 00:00 [revised]
PHST- 2010/04/09 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/08/19 06:00 [medline]
PHST- 2013/07/03 00:00 [pmc-release]
AID - S0047-6374(10)00075-8 [pii]
AID - 10.1016/j.mad.2010.04.004 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2010 May;131(5):354-63. doi: 10.1016/j.mad.2010.04.004. Epub 
      2010 Apr 24.