PMID- 33728029
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20240226
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2021
DP  - 2021
TI  - Resveratrol Confers Vascular Protection by Suppressing TLR4/Syk/NLRP3 Signaling 
      in Oxidized Low-Density Lipoprotein-Activated Platelets.
PG  - 8819231
LID - 10.1155/2021/8819231 [doi]
LID - 8819231
AB  - This study investigated the effect of resveratrol on Toll-like receptor 4- 
      (TLR4-) mediated matrix metalloproteinase 3 (MMP3) and MMP9 expression in 
      oxidized low-density lipoprotein- (ox-LDL-) activated platelets and the potential 
      molecule mechanism. Human platelets were used in the present study. The results 
      showed that resveratrol suppressed TLR4, MMP3, and MMP9 expression in 
      ox-LDL-activated platelets. The TLR4 inhibitor CLI-095 also inhibited MMP3 and 
      MMP9 expression and secretion in ox-LDL- and lipopolysaccharide- (LPS-) activated 
      platelets. The combination of resveratrol and CLI-095 synergistically suppressed 
      MMP3 and MMP9 expression in ox-LDL- and LPS-activated platelets. These findings 
      suggest that the resveratrol-induced inhibition of MMP3 and MMP9 expression is 
      linked to the suppression of TLR4 activation. Resveratrol also suppressed spleen 
      tyrosine kinase (Syk) phosphorylation and nucleotide-binding domain leucine-rich 
      repeat containing protein 3 (NLRP3) expression and IL-1beta secretion in ox-LDL- and 
      LPS-treated platelets. The coimmunoprecipitation results showed that resveratrol 
      inhibited the binding of Syk and NLRP3. Finally, resveratrol reduced vascular 
      senescence cells and the expression of TLR4, MMP3, and MMP9 and prevented 
      alterations of vascular structure in 52-week-old mice. Our findings demonstrated 
      that resveratrol decreased inflammatory protein expression and improved vascular 
      structure in aged mice. Resveratrol inhibited the expression of TLR4 and 
      secretion of MMP3, MMP9, and IL-1beta. The mechanism of action of resveratrol 
      appears to be associated with the inhibition of TLR4/Syk/NLRP3 activation in 
      ox-LDL-activated platelets.
CI  - Copyright (c) 2021 Yun Xue et al.
FAU - Xue, Yun
AU  - Xue Y
AUID- ORCID: 0000-0002-7714-5457
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
AD  - Graduate School of Peking Union Medical College, Beijing, China.
FAU - Chen, Huilian
AU  - Chen H
AUID- ORCID: 0000-0002-2344-0207
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Zhang, Shenghao
AU  - Zhang S
AUID- ORCID: 0000-0002-7752-334X
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Bao, Li
AU  - Bao L
AUID- ORCID: 0000-0002-4730-0970
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Chen, Beidong
AU  - Chen B
AUID- ORCID: 0000-0002-0561-7873
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Gong, Huan
AU  - Gong H
AUID- ORCID: 0000-0002-3942-8958
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Zhao, Yanyang
AU  - Zhao Y
AUID- ORCID: 0000-0001-5139-5311
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
FAU - Qi, Ruomei
AU  - Qi R
AUID- ORCID: 0000-0001-9611-1933
AD  - MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of 
      Gerontology, Beijing, China.
AD  - Graduate School of Peking Union Medical College, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20210225
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Sulfonamides)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Aging/pathology
MH  - Animals
MH  - Blood Platelets/drug effects/*metabolism
MH  - Caspase 1/metabolism
MH  - Cellular Senescence/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Drug Synergism
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - Lipoproteins, LDL/*pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Phosphorylation/drug effects
MH  - Platelet Activation/*drug effects
MH  - Protein Binding/drug effects
MH  - Resveratrol/*pharmacology
MH  - *Signal Transduction/drug effects
MH  - Sulfonamides/pharmacology
MH  - Syk Kinase/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Mice
PMC - PMC7935581
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2021/03/18 06:00
MHDA- 2021/05/21 06:00
PMCR- 2021/02/25
CRDT- 2021/03/17 06:48
PHST- 2020/09/04 00:00 [received]
PHST- 2021/02/04 00:00 [revised]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/03/17 06:48 [entrez]
PHST- 2021/03/18 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2021/02/25 00:00 [pmc-release]
AID - 10.1155/2021/8819231 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2021 Feb 25;2021:8819231. doi: 10.1155/2021/8819231. 
      eCollection 2021.