PMID- 28188730
OWN - NLM
STAT- MEDLINE
DCOM- 20170315
LR  - 20170315
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 173
DP  - 2017 Mar 15
TI  - Involvement of histone methylation in macrophage apoptosis and unstable plaque 
      formation in methionine-induced hyperhomocysteinemic ApoE(-/-) mice.
PG  - 135-144
LID - S0024-3205(17)30040-1 [pii]
LID - 10.1016/j.lfs.2017.02.003 [doi]
AB  - AIMS: Hyperhomocysteinemia (Hhcy) is an independent risk factor of 
      atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms 
      play an important role in the pathogenesis of atherosclerosis induced by Hhcy. 
      However, the exact mechanism is still undefined. Lesional apoptotic cells and 
      necrotic core formation contribute greatly to the progression of plaque. The 
      present study sought to determine whether modification of histone methylation is 
      involved in macrophage apoptosis and unstable plaque formation in the condition 
      of Hhcy. MATERIALS AND METHODS: The unstable plaque formation, lesional apoptotic 
      cells and status of histone methylation were monitored in the aortas of Hhcy 
      ApoE(-/-) mice induced by a high-methionine (HM) diet for 20weeks. Involvement of 
      histone methylation in macrophage apoptosis and foam cell formation were assessed 
      in macrophage Raw 264.7 cells after being challenged with homocysteine alone or 
      in combination with the histone methylation inhibitor BIX 01294. KEY FINDINGS: 
      The unstable plaque formation and lesion apoptotic cells are increased in 
      ApoE(-/)(-) mice supplemented with high-methionine (HM), accompanied with a 
      decreased expression of histone H3 lysine 9 dimethylation. Hhcy increases the 
      apoptosis of macrophages and inhibits the histone H3 lysine 9 dimethylation, as 
      well as the expression of histone methyltransferase G9a in vitro. Inhibition of 
      histone methylation by BIX01294 enhances macrophage apoptosis and foam cell 
      formation in vitro. SIGNIFICANCE: Our data suggest that Hhcy promotes the 
      progression of atherosclerosis via macrophage apoptosis. Histone methylation 
      might be involved in macrophage apoptosis and unstable plaque formation in 
      methionine induced hyperhomocysteinemic ApoE(-/-) mice.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Cong, Guangzhi
AU  - Cong G
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, PR China; Institute of Cardiovascular Diseases, General Hospital of 
      Ningxia Medical University, Yinchuan, Ningxia 750004, PR China.
FAU - Yan, Ru
AU  - Yan R
AD  - Institute of Cardiovascular Diseases, General Hospital of Ningxia Medical 
      University, Yinchuan, Ningxia 750004, PR China.
FAU - Huang, Hui
AU  - Huang H
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750004, PR China.
FAU - Wang, Kai
AU  - Wang K
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, PR China.
FAU - Yan, Ning
AU  - Yan N
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, PR China.
FAU - Jin, Ping
AU  - Jin P
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, PR China.
FAU - Zhang, Na
AU  - Zhang N
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 
      750001, PR China.
FAU - Hou, Jianjun
AU  - Hou J
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750004, PR China.
FAU - Chen, Dapeng
AU  - Chen D
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 
      750004, PR China.
FAU - Jia, Shaobin
AU  - Jia S
AD  - Institute of Cardiovascular Diseases, General Hospital of Ningxia Medical 
      University, Yinchuan, Ningxia 750004, PR China; Heart Centre, General Hospital of 
      Ningxia Medical University, Yinchuan, Ningxia 750004, PR China. Electronic 
      address: jsbxn@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170207
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Apolipoproteins E)
RN  - 0 (Histones)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/deficiency
MH  - Apoptosis/*drug effects
MH  - Disease Models, Animal
MH  - Histones/genetics/*metabolism
MH  - Hyperhomocysteinemia/*chemically induced/genetics/*metabolism
MH  - Methionine/*adverse effects/pharmacology
MH  - Methylation
MH  - Mice
MH  - Mice, Knockout
MH  - Plaque, Atherosclerotic/*chemically induced/genetics/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Atherosclerosis
OT  - Epigenomics
OT  - Histone methylation
OT  - Hyperhomocysteinemia
EDAT- 2017/02/12 06:00
MHDA- 2017/03/16 06:00
CRDT- 2017/02/12 06:00
PHST- 2016/11/19 00:00 [received]
PHST- 2017/01/18 00:00 [revised]
PHST- 2017/02/05 00:00 [accepted]
PHST- 2017/02/12 06:00 [pubmed]
PHST- 2017/03/16 06:00 [medline]
PHST- 2017/02/12 06:00 [entrez]
AID - S0024-3205(17)30040-1 [pii]
AID - 10.1016/j.lfs.2017.02.003 [doi]
PST - ppublish
SO  - Life Sci. 2017 Mar 15;173:135-144. doi: 10.1016/j.lfs.2017.02.003. Epub 2017 Feb 
      7.