PMID- 32768568
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 160
DP  - 2020 Nov 20
TI  - Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid 
      peroxidation and endothelial dysfunction in mouse aortic endothelial cell.
PG  - 92-102
LID - S0891-5849(20)31162-X [pii]
LID - 10.1016/j.freeradbiomed.2020.07.026 [doi]
AB  - Atherosclerosis (AS) is the fundamental pathological state of many serious 
      vascular diseases, characterized by disorders of lipid metabolism. Ferroptosis is 
      a type of regulated cell death that is mainly mediated by iron-dependent lipid 
      peroxidation. In this study, whether ferroptosis has occurred in AS and the 
      potential effects of ferroptosis on AS were investigated. Ferroptosis inhibitor 
      ferrostatin-1 (Fer-1) was administered to high-fat diet (HFD)-induced AS in 
      ApoE(-/-) mice. The results showed that Fer-1 could alleviate AS lesion in 
      HFD-fed ApoE(-/-) mice. Additionally, Fer-1 partially inhibited the iron 
      accumulation, lipid peroxidation and reversed the expressions of ferroptosis 
      indicators SLC7A11 and glutathione peroxidase 4 (GPX4) in HFD-fed ApoE(-/-) mice. 
      Next, we evaluated the effects of inhibition of ferroptosis on oxidized-low 
      density lipoprotein (ox-LDL)-induced mouse aortic endothelial cells (MAECs). 
      Results showed that Fer-1 increased cell viability and reduced cell death in 
      ox-LDL-treated MAECs. Moreover, Fer-1 decreased iron content and lipid 
      peroxidation and up-regulated the levels of SLC7A11 and GPX4. Additionally, Fer-1 
      down-regulated the expressions of adhesion molecules and up-regulated eNOS 
      expression. Iron chelator deferoxamine was used to demonstrate ferroptosis could 
      be partially inhibited by iron complexation in ox-LDL-treated MAECs. Our results 
      indicated that ferroptosis might occur during the initiation and development of 
      AS. More importantly, inhibition of ferroptosis could alleviate AS through 
      attenuating lipid peroxidation and endothelial dysfunction in AECs. Our findings 
      might contribute to a deeper understanding regarding the pathological process of 
      AS and provide a therapeutic target for AS.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Bai, Tao
AU  - Bai T
AD  - Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, 450052, PR China.
FAU - Li, Mingxing
AU  - Li M
AD  - Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, 450052, PR China.
FAU - Liu, Yuanfeng
AU  - Liu Y
AD  - Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, 450052, PR China.
FAU - Qiao, Zhentao
AU  - Qiao Z
AD  - Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, 450052, PR China.
FAU - Wang, Zhiwei
AU  - Wang Z
AD  - Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, 450052, PR China. Electronic address: 
      wangzhiwei126@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200805
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
SB  - IM
MH  - Animals
MH  - *Atherosclerosis/drug therapy
MH  - Cell Death
MH  - Endothelial Cells
MH  - *Ferroptosis
MH  - *Lipid Peroxidation
MH  - Mice
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Endothelial dysfunction
OT  - Ferroptosis
OT  - Lipid peroxidation
EDAT- 2020/08/10 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/04/16 00:00 [received]
PHST- 2020/06/24 00:00 [revised]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0891-5849(20)31162-X [pii]
AID - 10.1016/j.freeradbiomed.2020.07.026 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 Nov 20;160:92-102. doi: 
      10.1016/j.freeradbiomed.2020.07.026. Epub 2020 Aug 5.