PMID- 32325260
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20220531
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 301
DP  - 2020 May
TI  - TRPA1 regulates macrophages phenotype plasticity and atherosclerosis progression.
PG  - 44-53
LID - S0021-9150(20)30199-4 [pii]
LID - 10.1016/j.atherosclerosis.2020.04.004 [doi]
AB  - BACKGROUND AND AIMS: TRPA1 is a calcium permeable non-selective cation channel, 
      its expression is up-regulated in atherosclerosis plaque, yet its function in 
      macrophages activation is unknown. We sought to establish the role of TRPA1 in 
      inflammatory macrophages activation. METHODS: TRPA1(-/-)ApoE(-/-) mice and 
      C57BL/6 J control were treated with a high-fat diet (HFD) and the TRPA1 agonist 
      cinnamaldehyde (CIN). Third-order branches of superior aorta of patients and mice 
      were collected. Oil Red O staining and hematoxylin and eosin staining were 
      performed to measure atherosclerotic lesions. The RNA-seq was performed to 
      identify TRPA1 function in atherosclerosis. The expression of bone marrow-derived 
      macrophages (BMDMs) markers was tested by Western blot. In addition, the levels 
      of inflammatory factors were checked by ELISA. Chromatin immunoprecipitation 
      (ChIP)-PCR and luciferase reporter gene assays were used to explore if TRPA1 
      could regulate histone modifications. RESULTS: TRPA1(-/-)ApoE(-/-) mice showed a 
      significant increase in atherosclerosis plaques compared to ApoE(-/-) mice after 
      HFD treatment. Conversely, activation of TRPA1 by CIN sharply reduced 
      atherosclerosis progression. Atherosclerosis was associated with a significant 
      change in macrophage polarization toward the M1 proinflammatory phenotype. We 
      found that inhibition of TRPA1 remarkably stimulated M1 marker genes expression, 
      while repressed M2 marker genes expression. The interaction between TRPA1 and 
      Ezh2, a subunit of polycomb repressive complex 2, suppressed the 
      proteasome-dependent degradation of Ezh2. Thus, TRPA1 epigenetically regulated 
      H3K27 trimethylation level in macrophages. CONCLUSIONS: Our results demonstrate 
      that TRPA1, up-regulated in atherosclerosis plaque, could regulate the 
      macrophages toward an inflammatory phenotype, thereby modulating atherosclerosis 
      progression. Activation of TRPA1 might serve as an atherosclerosis therapeutic 
      target.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Wang, Qiang
AU  - Wang Q
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China.
FAU - Chen, Ken
AU  - Chen K
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Department of Nephrology, The General Hospital of Western Theater Command, 
      Chengdu, Sichuan, 610083, PR China.
FAU - Peng, Ke
AU  - Peng K
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China.
FAU - Yang, Dachun
AU  - Yang D
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China. Electronic address: yangdc71@126.com.
FAU - Yang, Yongjian
AU  - Yang Y
AD  - Department of Cardiology, The General Hospital of Western Theater Command, PR 
      China. Electronic address: yangyongjian38@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200413
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPA1 protein, human)
RN  - 0 (Trpa1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - *Atherosclerosis/genetics
MH  - Disease Models, Animal
MH  - Humans
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenotype
MH  - *Plaque, Atherosclerotic
MH  - TRPA1 Cation Channel/genetics
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Inflammation
OT  - Macrophages
OT  - TRPA1
COIS- Declaration of competing interest The authors declared they do not have anything 
      to disclose regarding conflict of interest with respect to this manuscript.
EDAT- 2020/04/24 06:00
MHDA- 2021/06/24 06:00
CRDT- 2020/04/24 06:00
PHST- 2019/07/01 00:00 [received]
PHST- 2020/03/23 00:00 [revised]
PHST- 2020/04/02 00:00 [accepted]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2020/04/24 06:00 [entrez]
AID - S0021-9150(20)30199-4 [pii]
AID - 10.1016/j.atherosclerosis.2020.04.004 [doi]
PST - ppublish
SO  - Atherosclerosis. 2020 May;301:44-53. doi: 10.1016/j.atherosclerosis.2020.04.004. 
      Epub 2020 Apr 13.