PMID- 37866313
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231227
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 125
IP  - Pt A
DP  - 2023 Dec
TI  - Depletion of beta-arrestin-1 in macrophages enhances atherosclerosis in ApoE(-/-) 
      mice.
PG  - 111085
LID - S1567-5769(23)01411-X [pii]
LID - 10.1016/j.intimp.2023.111085 [doi]
AB  - Autophagy in atherosclerotic plaque macrophage contributes to the alleviation of 
      atherosclerosis through the promotion of lipid metabolism. beta-arrestins are 
      multifunctional proteins participating various kinds of cellular signaling 
      pathways. Here we aimed to determine the role of beta-arrestin-1, an important 
      member of beta-arrestin family, in atherosclerosis, and whether autophagy was 
      involved in this process. ApoE(-/-)beta-arrestin-1(fl/fl)LysM-Cre mice were created 
      through bone marrow transplantation for the atherosclerosis model with 
      conditional myeloid knocking out beta-arrestin-1. Bone marrow-derived macrophages 
      (BMDMs) were used for the in vitro studies. Oil red O staining was used to detect 
      the lesional area. F4/80, Masson trichrome and picro-Sirius red staining were 
      applied for the determination of plaque stability. Real-time PCR was used for the 
      detection of levels of lipid metabolism-related receptors. Electron microscopy 
      and tandem fluorescent mRFP-GFP-LC3 plasmid was applied to test autophagy level. 
      We found that beta-arrestin-1 was highly increased in expression in plaque 
      macrophage on the occurrence of atherosclerosis. Conditional myeloid knocking out 
      beta-arrestin-1 largely promotes plaque formation and vulnerability. In murine 
      macrophage with lipid loading, knocking down beta-arrestin-1 enhanced foam cell 
      formation and levels of plasma and cellular cholesterol, while overexpressing 
      beta-arrestin-1 led to the opposite effects. The alleviative effects induced by 
      macrophage beta-arrestin-1 in atherosclerosis were involved in autophagy, based on 
      the reduction of autophagy level with the knocking down of macrophage 
      beta-arrestin-1 and administration of autophagy inhibitors which largely attenuated 
      the decreasing effect on foam cell formation. Our results demonstrated for the 
      first time that macrophage beta-arrestin-1 protected against atherosclerosis through 
      the induction of autophagy.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Shao, Bo-Zong
AU  - Shao BZ
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Liu, Meng-Zhen
AU  - Liu MZ
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Zhu, Dan-Ni
AU  - Zhu DN
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Yan, Hui
AU  - Yan H
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Ke, Ping
AU  - Ke P
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Wei, Wei
AU  - Wei W
AD  - State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and 
      Safety of Agro-products, Institute of Agro-Product Safety and Nutrition, Zhejiang 
      Academy of Agricultural Sciences, Hangzhou 310021, China.
FAU - Han, Ting
AU  - Han T
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China.
FAU - Liu, Chong
AU  - Liu C
AD  - Department of Pharmacy, Naval Medical University/Second Military Medical 
      University, Shanghai 200433 China. Electronic address: wanlc2004@aliyun.com.
LA  - eng
PT  - Journal Article
DEP - 20231020
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Apolipoproteins E)
RN  - 0 (beta-Arrestin 1)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Apolipoproteins E/genetics/metabolism
MH  - *Atherosclerosis/metabolism
MH  - Autophagy
MH  - *beta-Arrestin 1/genetics/metabolism
MH  - Macrophages/metabolism
MH  - *Plaque, Atherosclerotic
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Autophagy
OT  - Inflammation
OT  - Macrophage
OT  - beta-arrestin-1
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/23 00:43
MHDA- 2023/11/20 06:54
CRDT- 2023/10/22 18:13
PHST- 2023/07/12 00:00 [received]
PHST- 2023/10/12 00:00 [revised]
PHST- 2023/10/15 00:00 [accepted]
PHST- 2023/11/20 06:54 [medline]
PHST- 2023/10/23 00:43 [pubmed]
PHST- 2023/10/22 18:13 [entrez]
AID - S1567-5769(23)01411-X [pii]
AID - 10.1016/j.intimp.2023.111085 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Dec;125(Pt A):111085. doi: 
      10.1016/j.intimp.2023.111085. Epub 2023 Oct 20.