PMID- 24125430
OWN - NLM
STAT- MEDLINE
DCOM- 20140529
LR  - 20131015
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 231
IP  - 1
DP  - 2013 Nov
TI  - Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte 
      telomere length in atherosclerosis.
PG  - 173-9
LID - S0021-9150(13)00505-4 [pii]
LID - 10.1016/j.atherosclerosis.2013.08.029 [doi]
AB  - AIMS: Leukocyte telomere length (LTL) is shortened in patients with clinical 
      atherosclerosis (AS). Here we aimed to explore the contribution of elevated 
      homocysteine (Hcy) level to LTL shortening in AS patients and the underlying 
      mechanism. METHODS: Circulating leukocytes were collected from 197 patients with 
      AS and 165 sex- and age-matched healthy subjects for LTL determination. mRNA 
      expression or DNA methylation of human telomerase reverse transcriptase (hTERT) 
      was determined by real-time PCR and methylation-specific PCR assay, respectively. 
      We established a hyperhomocysteinemia (HHcy) mice model to confirm human results. 
      RESULTS: Hcy was negatively correlated with LTL shortening in AS patients (r = 
      -0.179, p = 0.015) and controls (r = -0.146, p = 0.031). Serum folate and 
      high-sensitivity C-reactive protein levels significantly interacted with Hcy in 
      LTL shortening. Hcy was related to hTERT mRNA downregulation and promoter 
      demethylation, which combined was associated with LTL shortening in AS patients. 
      Hcy-induced LTL shortening did not differ by sites of AS lesions or infarction. 
      Similar to clinical observations, our HHcy mice model suggested that Hcy induced 
      DNA demethylation and downregulation of mouse TERT and further contributed to LTL 
      shortening. CONCLUSIONS: Elevated Hcy level induced DNA demethylation of hTERT 
      and was closely related with hTERT downregulation, which led to LTL shortening in 
      AS. These findings provide novel insights into an epigenetic mechanism for 
      Hcy-related AS.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Zhang, Donghong
AU  - Zhang D
AD  - Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking 
      Union Medical College and Chinese Academy of Medical Sciences, 1 Shuaifuyuan, 
      Beijing 100730, China.
FAU - Wen, Xuemei
AU  - Wen X
FAU - Wu, Wei
AU  - Wu W
FAU - Xu, Ermu
AU  - Xu E
FAU - Zhang, Yujuan
AU  - Zhang Y
FAU - Cui, Wei
AU  - Cui W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130905
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
RN  - Homocysteinemia
SB  - IM
MH  - Animals
MH  - Atherosclerosis/genetics/metabolism
MH  - Epigenesis, Genetic
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/blood
MH  - Leukocytes/metabolism
MH  - Mice
MH  - Telomerase/*metabolism
MH  - Telomere/metabolism
MH  - *Telomere Shortening
OTO - NOTNLM
OT  - Atherosclerosis
OT  - DNA methyaltion
OT  - Homocysteine
OT  - Leukocyte
OT  - Telomere length
OT  - hTERT
EDAT- 2013/10/16 06:00
MHDA- 2014/05/30 06:00
CRDT- 2013/10/16 06:00
PHST- 2013/07/19 00:00 [received]
PHST- 2013/08/16 00:00 [revised]
PHST- 2013/08/26 00:00 [accepted]
PHST- 2013/10/16 06:00 [entrez]
PHST- 2013/10/16 06:00 [pubmed]
PHST- 2014/05/30 06:00 [medline]
AID - S0021-9150(13)00505-4 [pii]
AID - 10.1016/j.atherosclerosis.2013.08.029 [doi]
PST - ppublish
SO  - Atherosclerosis. 2013 Nov;231(1):173-9. doi: 
      10.1016/j.atherosclerosis.2013.08.029. Epub 2013 Sep 5.