PMID- 29673593
OWN - NLM
STAT- MEDLINE
DCOM- 20180919
LR  - 20180919
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 500
IP  - 2
DP  - 2018 Jun 2
TI  - Augmented neutrophil extracellular traps formation promotes atherosclerosis 
      development in socially defeated apoE(-/-) mice.
PG  - 490-496
LID - S0006-291X(18)30894-5 [pii]
LID - 10.1016/j.bbrc.2018.04.115 [doi]
AB  - Depression is an independent risk factor of cardiovascular disease (CVD); 
      however, the causal association remains undefined. We exposed mice to repeated 
      social defeat (RSD) to precipitate depressive-like behaviors, and investigated 
      the effects on atherosclerosis. Eight-week-old male apoE(-/-) mice were exposed 
      to RSD by housing with a larger CD-1 mouse in a shared home cage. They were 
      subjected to vigorous physical contact daily for 10 consecutive days and fed a 
      high-cholesterol diet (HCD) for 6 weeks. The social interaction ratio and 
      immobility time showed dramatic social avoidance before and after HCD feeding. 
      Defeated mice showed higher increase in atherosclerotic lesion areas in the 
      aortic root and entire aorta than control mice. Mean blood pressure and lipid 
      profile were equivalent in both groups. While Ly-6G- and Mac3-positive areas in 
      the aortic root were comparable between the groups, citrullinated histone H3 
      (Cit-H3)- and myeloperoxidase (MPO)-positive areas, markers of neutrophil 
      extracellular traps (NETs), were significantly increased in the defeated mice. 
      Treatment with DNase I completely diminished the exaggerated atherosclerosis. The 
      proportion of peripheral blood polymorphonuclear myeloid-derived suppressor cells 
      (PMN-MDSC), but not of inflammatory monocytes, was markedly increased. Moreover, 
      in vitro NETs formation from bone marrow (BM) PMN-MDSC was markedly augmented, 
      accompanied by higher expression of Nox2 gene and reactive oxygen species. Our 
      findings demonstrate that exposure to RSD promotes atherosclerosis by augmenting 
      NETs formation within the plaque. This provides new insight into the underlying 
      mechanism of depression-related CVD.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Yamamoto, Keita
AU  - Yamamoto K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Yamada, Hiroyuki
AU  - Yamada H
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan. Electronic address: 
      hiyamada@koto.kpu-m.ac.jp.
FAU - Wakana, Noriyuki
AU  - Wakana N
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Kikai, Masakazu
AU  - Kikai M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Terada, Kensuke
AU  - Terada K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Wada, Naotoshi
AU  - Wada N
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Motoyama, Shinichiro
AU  - Motoyama S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Saburi, Makoto
AU  - Saburi M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Sugimoto, Takeshi
AU  - Sugimoto T
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Kami, Daisuke
AU  - Kami D
AD  - Department of Regenerative Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Ogata, Takehiro
AU  - Ogata T
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Ibi, Masakazu
AU  - Ibi M
AD  - Department of Pharmacology, Graduate School of Medical Science, Kyoto Prefectural 
      University of Medicine, Kyoto, Japan.
FAU - Yabe-Nishimura, Chihiro
AU  - Yabe-Nishimura C
AD  - Department of Pharmacology, Graduate School of Medical Science, Kyoto Prefectural 
      University of Medicine, Kyoto, Japan.
FAU - Matoba, Satoaki
AU  - Matoba S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180419
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Apolipoproteins E)
RN  - EC 3.1.21.1 (Deoxyribonuclease I)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*deficiency/metabolism
MH  - Atherosclerosis/blood/*pathology
MH  - Bone Marrow/pathology
MH  - Cell Movement
MH  - Deoxyribonuclease I/metabolism
MH  - Extracellular Traps/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Myeloid-Derived Suppressor Cells/metabolism
MH  - Neutrophils/*metabolism
MH  - *Social Behavior
MH  - Stress, Psychological/pathology
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Depression
OT  - Myeloid-derived suppressor cells
OT  - NETosis
OT  - Neutrophils
EDAT- 2018/04/21 06:00
MHDA- 2018/09/20 06:00
CRDT- 2018/04/21 06:00
PHST- 2018/04/12 00:00 [received]
PHST- 2018/04/14 00:00 [accepted]
PHST- 2018/04/21 06:00 [pubmed]
PHST- 2018/09/20 06:00 [medline]
PHST- 2018/04/21 06:00 [entrez]
AID - S0006-291X(18)30894-5 [pii]
AID - 10.1016/j.bbrc.2018.04.115 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Jun 2;500(2):490-496. doi: 
      10.1016/j.bbrc.2018.04.115. Epub 2018 Apr 19.