PMID- 35618182
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20220708
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1868
IP  - 9
DP  - 2022 Sep 1
TI  - Loss of CD226 protects apolipoprotein E-deficient mice from diet-induced 
      atherosclerosis.
PG  - 166452
LID - S0925-4439(22)00122-3 [pii]
LID - 10.1016/j.bbadis.2022.166452 [doi]
AB  - CD226 is a costimulatory molecule that regulates immune cell functions in T 
      cells, natural killer cells, and macrophages. Because macrophage-derived foam 
      cell formation is a crucial factor contributing to the development of 
      atherosclerosis, we aimed to evaluate the potential roles of CD226 in the 
      pathogenesis of atherosclerosis. The effects of CD226 on atherosclerosis were 
      investigated in CD226 and apolipoprotein E double-knockout (CD226(-/-) ApoE(-/-)) 
      mice fed with a high-cholesterol atherogenic diet. CD226 expression in 
      macrophages was evaluated using flow cytometry. Histopathological analysis was 
      performed to evaluate the atherosclerotic lesions. Inflammatory cell infiltration 
      was detected using immunofluorescence staining. Bone marrow-derived macrophages 
      (BMDMs) and peritoneal macrophages (PEMs) were isolated from the mice and used to 
      explore the mechanism in vitro. The in vivo results indicated that CD226 
      knockdown protected against atherosclerosis in ApoE(-/-) mice, evidenced by 
      reduced plaque accumulation in the brachiocephalic artery, aortic roots, and main 
      aortic tree. CD226 gene-deficient macrophages showed reduced foam cell formation 
      under ox-low density lipoprotein stimulation compared with wild-type (WT) cells. 
      CD226 deficiency also decreased the expression of CD36 and scavenger receptor 
      (SR)-A (responsible for lipoprotein uptake) but increased the expression of 
      ATP-binding cassette transporter A1 and G1 (two transporters for cholesterol 
      efflux). Therefore, loss of CD226 hinders foam cell formation and atherosclerosis 
      progression, suggesting that CD226 is a promising new therapeutic target for 
      atherosclerosis.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Institute of Medical Research, Northwestern Polytechnical University, 127 West 
      Youyi Road, Xi'an, Shaanxi 710072, China.
FAU - Xu, Xuexue
AU  - Xu X
AD  - Institute of Medical Research, Northwestern Polytechnical University, 127 West 
      Youyi Road, Xi'an, Shaanxi 710072, China.
FAU - Ma, Jingchang
AU  - Ma J
AD  - Department of Immunology, Fourth Military Medical University, 169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Liu, Yongming
AU  - Liu Y
AD  - Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, 1 
      Xinsi Road, Xi'an, Shaanxi 710032, China.
FAU - Duan, Chujun
AU  - Duan C
AD  - Department of Immunology, Fourth Military Medical University, 169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Liu, Yitian
AU  - Liu Y
AD  - Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, 1 
      Xinsi Road, Xi'an, Shaanxi 710032, China.
FAU - Feng, Chongyang
AU  - Feng C
AD  - Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, 1 
      Xinsi Road, Xi'an, Shaanxi 710032, China.
FAU - Li, Wenpeng
AU  - Li W
AD  - Orthopedic Department of Tangdu Hospital, Fourth Military Medical University, 1 
      Xinsi Road, Xi'an, Shaanxi 710032, China.
FAU - Wang, Yuling
AU  - Wang Y
AD  - Department of Immunology, Fourth Military Medical University, 169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Cheng, Kun
AU  - Cheng K
AD  - Department of Immunology, Fourth Military Medical University, 169 West Changle 
      Road, Xi'an, Shaanxi 710032, China.
FAU - Zhuang, Ran
AU  - Zhuang R
AD  - Institute of Medical Research, Northwestern Polytechnical University, 127 West 
      Youyi Road, Xi'an, Shaanxi 710072, China; Department of Immunology, Fourth 
      Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, China. 
      Electronic address: fmmuzhr@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220523
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (Apolipoproteins E)
RN  - 0 (CD226 antigen)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation, T-Lymphocyte/*metabolism
MH  - Apolipoproteins E/metabolism
MH  - *Atherosclerosis/genetics/metabolism
MH  - *Cholesterol/metabolism
MH  - Diet
MH  - Foam Cells
MH  - Mice
OTO - NOTNLM
OT  - Atherosclerosis
OT  - CD226 gene knockout mice
OT  - Foam cell formation
OT  - Lipid metabolism
EDAT- 2022/05/27 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/05/26 19:26
PHST- 2021/10/16 00:00 [received]
PHST- 2022/04/18 00:00 [revised]
PHST- 2022/05/18 00:00 [accepted]
PHST- 2022/05/27 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/05/26 19:26 [entrez]
AID - S0925-4439(22)00122-3 [pii]
AID - 10.1016/j.bbadis.2022.166452 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2022 Sep 1;1868(9):166452. doi: 
      10.1016/j.bbadis.2022.166452. Epub 2022 May 23.