PMID- 19090788
OWN - NLM
STAT- MEDLINE
DCOM- 20090706
LR  - 20181201
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 116
IP  - 11
DP  - 2009 May 1
TI  - Effect of intensive lipid-lowering therapy on telomere erosion in endothelial 
      progenitor cells obtained from patients with coronary artery disease.
PG  - 827-35
LID - 10.1042/CS20080404 [doi]
AB  - Telomere erosion of EPCs (endothelial progenitor cells) may be a key factor in 
      endothelial cell senescence and is highly dependent on cellular oxidative damage. 
      The aim of the present study was to investigate whether LLT (lipid-lowering 
      therapy) with statins could attenuate EPC telomere erosion in patients with CAD 
      (coronary artery disease). The study included 100 patients with stable CAD and 25 
      subjects without CAD as controls. CAD patients were randomized to 12 months of 
      intensive LLT with atorvastatin or moderate LLT with pravastatin. EPCs were 
      obtained from peripheral blood at baseline and after 12 months of statin therapy. 
      Telomere length in EPCs was measured by FISH (fluorescence in situ hybridization) 
      and oxidative DNA damage by flow cytometry of oxidized DNA bases. EPC telomere 
      length was shorter in the CAD group than in the controls, and oxidative DNA 
      damage to EPCs was higher in the CAD group compared with controls. After 12 
      months of therapy, changes in lipid profiles were greater in the intensive LLT 
      group than in the moderate LLT group. Intensive LLT markedly increased EPC number 
      and decreased oxidative DNA damage in EPCs (both P<0.05), with no change in 
      telomere length. In contrast, moderate LLT did not change EPC counts or oxidative 
      DNA damage, but showed telomere shortening (P<0.05). There was a weak negative 
      correlation between changes in EPC number and LDL (low-density 
      lipoprotein)-cholesterol levels after intensive LLT, whereas there was no 
      correlation between them after moderate LLT. With in vitro culturing of EPCs 
      subjected to oxidative stress, atorvastatin led to the prevention of EPC telomere 
      shortening compared with pravastatin. In conclusion, the present study has 
      demonstrated that intensive LLT may prevent EPC telomere erosion in patients with 
      CAD, possibly contributing to the beneficial effects of intensive LLT in this 
      disorder.
FAU - Satoh, Mamoru
AU  - Satoh M
AD  - Division of Cardiology and Memorial Heart Center, Department of Internal 
      Medicine, Iwate Medical University School of Medicine, Morioka 020-8505, Iwate, 
      Japan. m_satoh@imu.ncvc.go.jp
FAU - Minami, Yoshitaka
AU  - Minami Y
FAU - Takahashi, Yuji
AU  - Takahashi Y
FAU - Tabuchi, Tsuyoshi
AU  - Tabuchi T
FAU - Itoh, Tomonori
AU  - Itoh T
FAU - Nakamura, Motoyuki
AU  - Nakamura M
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090501
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Pyrroles)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - A0JWA85V8F (Atorvastatin)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Anticholesteremic Agents/*therapeutic use
MH  - Atorvastatin
MH  - Cell Count
MH  - Cells, Cultured
MH  - Cholesterol/blood
MH  - Coronary Artery Disease/*drug therapy/pathology
MH  - Endothelial Cells/pathology
MH  - Female
MH  - Heptanoic Acids/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pravastatin/*therapeutic use
MH  - Prospective Studies
MH  - Pyrroles/*therapeutic use
MH  - Single-Blind Method
MH  - Stem Cells/*pathology
MH  - Telomere/*drug effects/pathology
EDAT- 2008/12/19 09:00
MHDA- 2009/07/07 09:00
CRDT- 2008/12/19 09:00
PHST- 2008/12/19 09:00 [entrez]
PHST- 2008/12/19 09:00 [pubmed]
PHST- 2009/07/07 09:00 [medline]
AID - CS20080404 [pii]
AID - 10.1042/CS20080404 [doi]
PST - epublish
SO  - Clin Sci (Lond). 2009 May 1;116(11):827-35. doi: 10.1042/CS20080404.