PMID- 37133566
OWN - NLM
STAT- MEDLINE
DCOM- 20230505
LR  - 20230517
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 80
IP  - 5
DP  - 2023 May 3
TI  - TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis.
PG  - 137
LID - 10.1007/s00018-023-04786-9 [doi]
AB  - Disordered lipid accumulation in the arterial wall is a hallmark of 
      atherosclerosis. Previous studies found that the expression of triggering 
      receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor of the 
      immunoglobulin family, is increased in mouse atherosclerotic aortic plaques. 
      However, it remains unknown whether TREM2 plays a role in atherosclerosis. Here 
      we investigated the role of TREM2 in atherosclerosis using ApoE knockout 
      (ApoE(-/-)) mouse models, primary vascular smooth muscle cells (SMCs), and bone 
      marrow-derived macrophages (BMDMs). In ApoE(-/-) mice, the density of 
      TREM2-positive foam cells in aortic plaques increased in a time-dependent manner 
      after the mice were fed a high-fat diet (HFD). Compared with ApoE(-/-) mice, the 
      Trem2(-/-)/ApoE(-/-) double-knockout mice showed significantly reduced 
      atherosclerotic lesion size, foam cell number, and lipid burden degree in plaques 
      after HFD feeding. Overexpression of TREM2 in cultured vascular SMCs and 
      macrophages exacerbates lipid influx and foam cell formation by upregulating the 
      expression of the scavenger receptor CD36. Mechanistically, TREM2 inhibits the 
      phosphorylation of p38 mitogen-activated protein kinase and peroxisome 
      proliferator activated-receptor gamma (PPARgamma), thereby increasing PPARgamma nuclear 
      transcriptional activity and subsequently promoting the transcription of CD36. 
      Our results indicate that TREM2 exacerbates atherosclerosis development by 
      promoting SMC- and macrophage-derived foam cell formation by regulating scavenger 
      receptor CD36 expression. Thus, TREM2 may act as a novel therapeutic target for 
      the treatment of atherosclerosis.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Guo, Xiaoqing
AU  - Guo X
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Li, Bowei
AU  - Li B
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Wen, Cheng
AU  - Wen C
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Xiang, Xuying
AU  - Xiang X
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Nie, Lei
AU  - Nie L
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Chen, Jiaojiao
AU  - Chen J
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Mao, Ling
AU  - Mao L
AUID- ORCID: 0000-0002-6442-3411
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China. maoling@hust.edu.cn.
LA  - eng
GR  - 81974182/National Natural Science Foundation of China/
GR  - 82171325/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230503
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (PPAR gamma)
RN  - 0 (CD36 Antigens)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Trem2 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Foam Cells/metabolism/pathology
MH  - PPAR gamma/genetics/metabolism
MH  - *Atherosclerosis/metabolism
MH  - *Plaque, Atherosclerotic/metabolism
MH  - Mice, Knockout
MH  - CD36 Antigens/genetics/metabolism
MH  - Cholesterol/metabolism
MH  - Apolipoproteins E/genetics/metabolism
MH  - Lipids
MH  - Lipoproteins, LDL/metabolism
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - Receptors, Immunologic/genetics/metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Cholesterol uptake
OT  - Foam cell
OT  - Lipid metabolism
OT  - TREM2
EDAT- 2023/05/03 12:42
MHDA- 2023/05/05 06:42
CRDT- 2023/05/03 11:07
PHST- 2022/12/05 00:00 [received]
PHST- 2023/04/24 00:00 [accepted]
PHST- 2023/04/09 00:00 [revised]
PHST- 2023/05/05 06:42 [medline]
PHST- 2023/05/03 12:42 [pubmed]
PHST- 2023/05/03 11:07 [entrez]
AID - 10.1007/s00018-023-04786-9 [pii]
AID - 10.1007/s00018-023-04786-9 [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2023 May 3;80(5):137. doi: 10.1007/s00018-023-04786-9.