PMID- 30899381
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 11
IP  - 2
DP  - 2019
TI  - SXBX pill suppresses homocysteine-induced vascular smooth muscle cells 
      dedifferentiation by inhibiting NLRP3 inflammasomes activation via ERK/p38 MAPK 
      pathways.
PG  - 806-818
AB  - The dedifferentiation of vascular smooth muscle cells (VSMCs) is a key event in 
      the pathogenesis of vascular remodeling-related disease. The present study aimed 
      to investigate the effects of shexiangbaoxin (SXBX) pill, a traditional Chinese 
      medicinal formula on VSMCs dedifferentiation and its potential mechanisms. 
      High-fat diet (HFD) was introduced to lipoprotein receptor-deficient (LDLR(-/-)) 
      mice to generate hyperhomocysteinemia (HHcy), and plasma Hcy and lipid levels 
      were analyzed. The phenotype of VSMCs was assessed in mice with the treatment of 
      low (45 mg/kg/d) or high (90 mg/kg/d) SXBX pill by measuring the contractile 
      protein alpha-SMA, SM22alpha and synthetic proteins OPN using RT-qPCR, western blotting 
      and immunofluorescence assay. In vitro, the proliferation, migration and 
      dedifferentiation of VSMCs were measured by MTT, Edu incorporation, wound healing 
      and western blotting assay. Small interfering RNA technology was used to examine 
      the role of NLRP3 in the effects of SXBX pill on dedifferentiation. The results 
      indicated that although SXBX pill had no influence on HFD-induced HHcy and 
      hyperlipidaemia, it reversed HHcy-induced dedifferentiation of VSMCs in vivo. 
      SXBX pill significantly inhibited proliferation, migration and dedifferentiation 
      of Hcy-treated VSMCs. In addition, we found that Hcy activated NLRP3 
      inflammasomes in VSMCs and SXBX pill could attenuate NLRP3 inflammasomes 
      activation. Moreover, subsequent analysis suggested that SXBX pill inhibited 
      NLRP3 inflammasomes activation through regulation of ERK1/2 and p38 MAPK pathway. 
      Knockdown of NLRP3 reversed the inhibitory effects of SXBX pill in VSMCs. In 
      conclusion, SXBX pill inhibited Hcy-induced proliferation, migration and 
      dedifferentiation of VSMCs by suppressing NLRP3 inflammasomes activation via of 
      ERK/p38 MAPK pathway.
FAU - Liu, Long Bin
AU  - Liu LB
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
AD  - Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang 
      University School of Medicine) Shaoxing 312000, Zhejiang Province, China.
FAU - Shen, Hong Feng
AU  - Shen HF
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
FAU - Cha, Wei
AU  - Cha W
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
FAU - Jin, Zhi Jiang
AU  - Jin ZJ
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
FAU - Xia, Hai Jiang
AU  - Xia HJ
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
FAU - Liu, Jing Jing
AU  - Liu JJ
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
FAU - Hu, Jia Feng
AU  - Hu JF
AD  - Department of Cardiology, The Affiliated Hospital of Shaoxing University 
      Shaoxing, Zhejiang Province, China.
AD  - Department of Cardiology, Shaoxing Municipal Hospital Shaoxing, Zhejiang 
      Province, China.
LA  - eng
PT  - Journal Article
DEP - 20190215
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC6413280
OTO - NOTNLM
OT  - NLRP3 inflammasomes
OT  - SXBX pill
OT  - dedifferentiation
OT  - homocysteine
OT  - vascular smooth muscle cell
COIS- None.
EDAT- 2019/03/23 06:00
MHDA- 2019/03/23 06:01
PMCR- 2019/02/15
CRDT- 2019/03/23 06:00
PHST- 2018/10/13 00:00 [received]
PHST- 2018/12/28 00:00 [accepted]
PHST- 2019/03/23 06:00 [entrez]
PHST- 2019/03/23 06:00 [pubmed]
PHST- 2019/03/23 06:01 [medline]
PHST- 2019/02/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2019 Feb 15;11(2):806-818. eCollection 2019.