PMID- 34478920
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20211026
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 334
DP  - 2021 Oct
TI  - The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and 
      vulnerable plaque formation in atherosclerosis.
PG  - 39-47
LID - S0021-9150(21)01276-4 [pii]
LID - 10.1016/j.atherosclerosis.2021.08.015 [doi]
AB  - BACKGROUND AND AIMS: Hyperhomocysteinemia (HHcy) is an independent risk factor 
      for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by 
      endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of 
      HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1alpha (Ero1alpha) 
      is critical for ER stress-induced apoptosis. We hypothesized that Ero1alpha may 
      contribute to ER-stress induced macrophage apoptosis and plaque stability in 
      advanced atherosclerotic lesions by HHcy. METHODS: Apoe(-/-) mice were maintained 
      on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy 
      atherosclerotic models. The role of Ero1alpha in atherosclerotic plaque stability, 
      macrophage apoptosis and ER stress were monitored in the plaque of aortic roots 
      in HHcy Apoe(-/-) mice with or without silence or overexpression of Ero1alpha through 
      lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of 
      Ero1alpha on ER stress dependent apoptosis in the presence of HHcy. RESULTS: 
      Atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in 
      Apoe(-/-) mice by high Hcy diet, accompanied by the upregulation of Ero1alpha 
      expression and ER stress. Inhibition of Ero1alpha prevented macrophage apoptosis and 
      atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse 
      peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1alpha 
      deficiency, but enhanced by Ero1alpha overexpression. CONCLUSIONS: Hcy, via 
      upregulation of Ero1alpha expression, activates ER stress-dependent macrophage 
      apoptosis to promote vulnerable plaque formation in atherosclerosis. Ero1alpha may be 
      a potential therapeutic target for atherosclerosis induced by Hcy.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Zhang, Na
AU  - Zhang N
AD  - Department of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China.
FAU - Zhu, Lili
AU  - Zhu L
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China.
FAU - Wu, Xianxian
AU  - Wu X
AD  - Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences 
      (CAMS) & Peking Union Medical Collage (PUMC), Beijing, 100021, PR China.
FAU - Yan, Ru
AU  - Yan R
AD  - Institute of Cardiovascular Diseases, General Hospital of Ningxia Medical 
      University, Yinchuan, Ningxia, 750001, PR China.
FAU - Yang, Shaobing
AU  - Yang S
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China.
FAU - Jiang, Xiaoliang
AU  - Jiang X
AD  - Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences 
      (CAMS) & Peking Union Medical Collage (PUMC), Beijing, 100021, PR China.
FAU - Liu, Xing
AU  - Liu X
AD  - Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences 
      (CAMS) & Peking Union Medical Collage (PUMC), Beijing, 100021, PR China.
FAU - Liu, Xue
AU  - Liu X
AD  - Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences 
      (CAMS) & Peking Union Medical Collage (PUMC), Beijing, 100021, PR China.
FAU - Yan, Ning
AU  - Yan N
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China.
FAU - Cong, Guangzhi
AU  - Cong G
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China.
FAU - Yang, Zhiwei
AU  - Yang Z
AD  - Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences 
      (CAMS) & Peking Union Medical Collage (PUMC), Beijing, 100021, PR China. 
      Electronic address: yangzhiwei@cnilas.pumc.edu.cn.
FAU - Jia, Shaobin
AU  - Jia S
AD  - Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 
      750001, PR China; Institute of Cardiovascular Diseases, General Hospital of 
      Ningxia Medical University, Yinchuan, Ningxia, 750001, PR China. Electronic 
      address: jsbxn@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210811
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Apoptosis
MH  - *Atherosclerosis/genetics
MH  - Endoplasmic Reticulum Stress
MH  - *Homocysteine
MH  - Macrophages, Peritoneal
MH  - Mice
OTO - NOTNLM
OT  - Endoplasmic reticulum oxidoreductase 1alpha
OT  - Endoplasmic reticulum stress
OT  - Hyperhomocysteinemia
OT  - Macrophage apoptosis
OT  - Vulnerable plaque
EDAT- 2021/09/04 06:00
MHDA- 2021/10/27 06:00
CRDT- 2021/09/03 20:15
PHST- 2021/01/16 00:00 [received]
PHST- 2021/07/28 00:00 [revised]
PHST- 2021/08/10 00:00 [accepted]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2021/09/03 20:15 [entrez]
AID - S0021-9150(21)01276-4 [pii]
AID - 10.1016/j.atherosclerosis.2021.08.015 [doi]
PST - ppublish
SO  - Atherosclerosis. 2021 Oct;334:39-47. doi: 10.1016/j.atherosclerosis.2021.08.015. 
      Epub 2021 Aug 11.