PMID- 37309064
OWN - NLM
STAT- MEDLINE
DCOM- 20230808
LR  - 20230808
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 47
IP  - 9
DP  - 2023 Sep
TI  - Macrophage Gpx4 deficiency aggravates foam cell formation by regulating the 
      expression of scavenger receptors, ABCA1, and ABCG1.
PG  - 1589-1599
LID - 10.1002/cbin.12057 [doi]
AB  - Macrophage-derived foam cell formation is critical for the initiation and 
      development of atherosclerosis, which contributes to atherosclerotic 
      cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial 
      ferroptosis regulator, protects cells from excessive oxidative stress by 
      neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam 
      cell formation remains unknown. We reported that oxidized low-density lipoprotein 
      (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre-loxP system, we 
      generated myeloid cell-specific Gpx4 knockout (Gpx4(myel-KO) ) mice. Bone 
      marrow-derived macrophages (BMDMs) were isolated from WT and Gpx4(myel-KO) mice 
      and incubated with modified low-density lipoprotein (LDL). We found that Gpx4 
      deficiency promoted foam cell formation and increased the internalization of 
      modified LDL. Mechanistic studies unveiled that Gpx4 knockout upregulated 
      scavenger receptor type A and LOX-1 expression and downregulated ABCA1 and ABCG1 
      expression. Collectively, our study lends a novel insight into the role of GPX4 
      in suppressing macrophage-derived foam cell formation and suggests GPX4 as a 
      promising therapeutic target to interfere with atherosclerosis-related diseases.
CI  - (c) 2023 International Federation of Cell Biology.
FAU - Zhou, Jingquan
AU  - Zhou J
AUID- ORCID: 0000-0002-2082-6112
AD  - The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's 
      Hospital, Qingyuan, China.
AD  - Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & 
      Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      Guangdong, China.
FAU - Wu, Suhua
AU  - Wu S
AD  - Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & 
      Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      Guangdong, China.
FAU - Chen, Xiaoqin
AU  - Chen X
AD  - Guangzhou Kingmed Center for Clinical Laboratory, Guangzhou, Guangdong, China.
FAU - Hou, Lianjie
AU  - Hou L
AD  - The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's 
      Hospital, Qingyuan, China.
FAU - Zhong, Qiong
AU  - Zhong Q
AD  - The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's 
      Hospital, Qingyuan, China.
FAU - Luo, Weixia
AU  - Luo W
AD  - The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's 
      Hospital, Qingyuan, China.
FAU - Dai, Chunni
AU  - Dai C
AD  - Zhangjiajie Center for Disease Control and Prevention, Zhangjiajie, Hunan, China.
FAU - Dai, Xiaoyan
AU  - Dai X
AUID- ORCID: 0000-0001-5695-6384
AD  - Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & 
      Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      Guangdong, China.
LA  - eng
GR  - 81974046/National Natural Science Foundation of China/
GR  - 82170467/National Natural Science Foundation of China/
GR  - 2022A1515012502/Natural Science Foundation of Guangdong Province/
GR  - 202201-301/Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 
      People's Hospital/
PT  - Journal Article
DEP - 20230612
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, Scavenger)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ABCA1 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Foam Cells/metabolism
MH  - Macrophages/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Receptors, Scavenger/metabolism
MH  - *Atherosclerosis/metabolism
MH  - ATP Binding Cassette Transporter 1/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/metabolism
OTO - NOTNLM
OT  - ABCA1
OT  - ABCG1
OT  - GPX4
OT  - foam cell
OT  - macrophage
OT  - scavenger receptor
EDAT- 2023/06/13 06:42
MHDA- 2023/08/08 06:42
CRDT- 2023/06/13 00:33
PHST- 2023/03/28 00:00 [revised]
PHST- 2022/12/08 00:00 [received]
PHST- 2023/05/31 00:00 [accepted]
PHST- 2023/08/08 06:42 [medline]
PHST- 2023/06/13 06:42 [pubmed]
PHST- 2023/06/13 00:33 [entrez]
AID - 10.1002/cbin.12057 [doi]
PST - ppublish
SO  - Cell Biol Int. 2023 Sep;47(9):1589-1599. doi: 10.1002/cbin.12057. Epub 2023 Jun 
      12.