PMID- 37251076
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230531
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 10
DP  - 2023
TI  - Toll-like receptor 4 deficiency in mice impairs venous thrombus resolution.
PG  - 1165589
LID - 10.3389/fmolb.2023.1165589 [doi]
LID - 1165589
AB  - Objective: Toll-like receptor 4 (TLR4) is crucial to the development of sterile 
      inflammatory responses. The deep venous thrombosis resolution (DVT) is similar to 
      sterile inflammation, so we hypothesize that TLR4 is involved. Methods and 
      Results: We evaluated the effects of TLR4 deficiency on thrombus lysis in vivo, 
      and explored the mechanisms in vitro. DVT mouse model was established by inferior 
      vena cava (IVC) ligation. After the IVC ligation (1, 3, and 7 d), the mice were 
      euthanized to collect the venous thrombus. The Tlr4-/- mice had significantly 
      elevated weight/length ratios of thrombi at 3 and 7 d and increased collagen 
      content at 3 d after IVC ligation, in addition to significantly lesser 
      intrathrombus infiltration of neutrophils and macrophages, lower monocyte 
      chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) 
      expression in thrombus tissue sections and homogenates, and lower pro-MMP-9 
      activity at 3 d after IVC ligation than wild-type mice. After 7 days of IVC 
      ligation, VEGF, IFNbeta, and MCP-5 protein expression were decreased in venous 
      thrombus from Tlr4-/- mice. 2 ml of 3% thioglycolate was injected 
      intraperitoneally and peritoneal exudate was collected 3 days later from Tlr4-/- 
      and wild type mice respectively. The intraperitoneal macrophages were isolated 
      from adherent culture after centrifugation. Lipopolysaccharide (LPS) can activate 
      TLR4/NF-kappaB signalling pathway in a concentration-dependent manner, initiated p65 
      nuclear translocation, IkappaBalpha phosphorylation and degradation, MMP-9 and MCP-1 
      transcription in WT intraperitoneal macrophages but not in Tlr4-/- 
      intraperitoneal macrophages. Conclusion: TLR4 is involved in venous thrombosis 
      resolution through NF-kappaB pathway. Loss of TLR4 in mice impairs the process.
CI  - Copyright (c) 2023 Yuan, Huang and Ding.
FAU - Yuan, Haixin
AU  - Yuan H
AD  - Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Huang, Xiaoxi
AU  - Huang X
AD  - Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Ding, Jie
AU  - Ding J
AD  - Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20230512
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC10213506
OTO - NOTNLM
OT  - NF-kappaB
OT  - TLR4
OT  - macrophages
OT  - mice
OT  - venous thrombus resolution
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/30 13:07
MHDA- 2023/05/30 13:08
PMCR- 2023/01/01
CRDT- 2023/05/30 11:32
PHST- 2023/02/14 00:00 [received]
PHST- 2023/04/13 00:00 [accepted]
PHST- 2023/05/30 13:08 [medline]
PHST- 2023/05/30 13:07 [pubmed]
PHST- 2023/05/30 11:32 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 1165589 [pii]
AID - 10.3389/fmolb.2023.1165589 [doi]
PST - epublish
SO  - Front Mol Biosci. 2023 May 12;10:1165589. doi: 10.3389/fmolb.2023.1165589. 
      eCollection 2023.