PMID- 36064133
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221206
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1868
IP  - 12
DP  - 2022 Dec 1
TI  - Inhibition of macrophage-derived foam cells by Adipsin attenuates progression of 
      atherosclerosis.
PG  - 166533
LID - S0925-4439(22)00204-6 [pii]
LID - 10.1016/j.bbadis.2022.166533 [doi]
AB  - Phagocytosis of oxidized low-density lipoprotein (OxLDL) by macrophages yields 
      "foam cells" and serves as a hallmark of atherosclerotic lesion. Adipsin is a 
      critical component of the complement activation pathway. Recent evidence has 
      indicated an obligatory role for Adipsin in pathological models including 
      ischemia-reperfusion and sepsis. Adipsin levels are significantly decreased in 
      patients with asymptomatic carotid atherosclerosis, implying the role for Adipsin 
      as a potential marker of asymptomatic carotid atherosclerosis. This study was 
      designed to evaluate the role for Adipsin in atherosclerosis and the mechanisms 
      involved using both in vivo and in vitro experiments. ApoE(-/-)/AdipsinTg mice 
      were constructed and were fed a high-fat diet for 12 weeks. Compared with 
      ApoE(-/-) mice, area of the sclerotic plaques was reduced, along with lower 
      macrophage deposition within the plaque in ApoE(-/-)/AdipsinTg mice. RAW264.7 
      cells and bone marrow-derived macrophages (BMDMs) were stimulated with oxLDL 
      (50 mug/ml). Adenovirus vectors containing the Adipsin gene were transfected into 
      macrophages. Lipid accumulation was observed by Oil red O staining. Western blot 
      and reverse transcription-polymerase chain reaction data revealed that Adipsin 
      overexpression inhibited oxLDL-induced lipid uptake and foam cell formation and 
      upregulation of CD36 and PPARgamma in Ad-Adipsin-transfected macrophages. In 
      addition, the PPARgamma-specific agonist GW1929 reversed Adipsin 
      overexpression-evoked inhibitory effect on lipid uptake. These results 
      demonstrate unequivocally that Adipsin inhibits lipid uptake in a 
      PPARgamma/CD36-dependent manner and prevents the formation of foam cells, implying 
      that Adipsin may be a potential therapeutic target against atherosclerosis.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Duan, Yu
AU  - Duan Y
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Zhang, Xuebin
AU  - Zhang X
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Lin, Jie
AU  - Lin J
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Shu, Xiaofei
AU  - Shu X
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Man, Wanrong
AU  - Man W
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Jiang, Mengyuan
AU  - Jiang M
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Wu, Dexi
AU  - Wu D
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Zhao, Zhijing
AU  - Zhao Z
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China.
FAU - Sun, Dongdong
AU  - Sun D
AD  - Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, China. Electronic address: 51483696@qq.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220905
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Apolipoproteins E)
RN  - 0 (CD36 Antigens)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (PPAR gamma)
RN  - EC 3.4.21.46 (Complement Factor D)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics/metabolism
MH  - *Atherosclerosis/metabolism
MH  - CD36 Antigens/metabolism
MH  - *Carotid Artery Diseases/metabolism/pathology
MH  - Complement Factor D/genetics/metabolism
MH  - Foam Cells
MH  - Lipoproteins, LDL/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - PPAR gamma/metabolism
MH  - *Plaque, Atherosclerotic/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Adipsin
OT  - Atherosclerosis
OT  - CD36
OT  - Foam cell formation
OT  - Macrophage
OT  - PPRAgamma
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- 2022/09/06 06:00
MHDA- 2022/10/19 06:00
CRDT- 2022/09/05 19:27
PHST- 2022/06/12 00:00 [received]
PHST- 2022/08/03 00:00 [revised]
PHST- 2022/08/23 00:00 [accepted]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/09/05 19:27 [entrez]
AID - S0925-4439(22)00204-6 [pii]
AID - 10.1016/j.bbadis.2022.166533 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2022 Dec 1;1868(12):166533. doi: 
      10.1016/j.bbadis.2022.166533. Epub 2022 Sep 5.