PMID- 34135690
OWN - NLM
STAT- MEDLINE
DCOM- 20211222
LR  - 20220424
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2021
DP  - 2021
TI  - The Inflammasome Signaling Pathway Is Actively Regulated and Related to 
      Myocardial Damage in Coronary Thrombi from Patients with STEMI.
PG  - 5525917
LID - 10.1155/2021/5525917 [doi]
LID - 5525917
AB  - BACKGROUND: The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the 
      Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response 
      in myocardial reperfusion injury. Expanding our knowledge about the inflammasome 
      signaling axis is important to improve treatment options. In a cross-sectional 
      study, we aimed to study presence, localization, and genetic expression of 
      inflammasome- and IL-6- signaling-related proteins in coronary thrombi and 
      circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, 
      with relation to myocardial injury and time from symptoms to PCI. METHODS: 
      Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were 
      drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1beta 
      (IL1-beta), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 
      130 (gp130) were isolated from thrombi and circulating leukocytes and relatively 
      quantified by RT-PCR. A part of each thrombus was embedded in paraffin for 
      histology and immunohistochemistry analyses. RESULTS: Genes encoding the 8 
      markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi 
      significantly correlated to troponin T (r = 0.455, p = 0.013), as did NLRP3 (r = 
      0.468, p = 0.024). Troponin T correlated with expression in circulating 
      leukocytes of TLR4 (r = 0.438, p = 0.011), NLRP3 (r = 0.420, p = 0.0149), and 
      IL-1beta (r = 0.394, p = 0.023). IL-6R expression in thrombi correlated 
      significantly to troponin T (r = 0.434, p = 0.019), whereas gp130 was inversely 
      correlated (r = -0.398, p = 0.050). IL-6 in circulating leukocytes correlated 
      inversely to troponin T (r = -0.421, p = 0.015). There were no significant 
      correlations between genes expressed in thrombi and time from symptom to PCI. 
      CONCLUSIONS: The inflammasome signaling pathway was actively regulated in 
      coronary thrombi and in circulating leukocytes from patients with STEMI, in 
      association with myocardial damage measured by troponin T. This supports the 
      strategy of medically targeting this pathway in treating myocardial infarction 
      and contributes to sort out optimal timing and targets for anti-inflammatory 
      treatment. The study is registered at clinicaltrials.gov with identification 
      number NCT02746822.
CI  - Copyright (c) 2021 Jostein Nordeng et al.
FAU - Nordeng, Jostein
AU  - Nordeng J
AUID- ORCID: 0000-0001-9680-9688
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
AD  - Department of Cardiology, Oslo University Hospital Ulleval, Norway.
AD  - Faculty of Medicine, University of Oslo, Norway.
FAU - Schandiz, Hossein
AU  - Schandiz H
AUID- ORCID: 0000-0002-2517-6382
AD  - Department of Pathology, Akershus University Hospital, Norway.
FAU - Solheim, Svein
AU  - Solheim S
AUID- ORCID: 0000-0003-3321-6572
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
AD  - Department of Cardiology, Oslo University Hospital Ulleval, Norway.
FAU - Akra, Sissel
AU  - Akra S
AUID- ORCID: 0000-0003-4068-2192
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
FAU - Hoffman, Pavel
AU  - Hoffman P
AUID- ORCID: 0000-0003-1287-9174
AD  - Section for Interventional Cardiology, Department of Cardiology, Oslo University 
      Hospital Ulleval, Norway.
FAU - Roald, Borghild
AU  - Roald B
AUID- ORCID: 0000-0003-2698-2586
AD  - Faculty of Medicine, University of Oslo, Norway.
AD  - Department of Pathology, Oslo University Hospital Ulleval, Norway.
FAU - Bendz, Bjorn
AU  - Bendz B
AUID- ORCID: 0000-0002-1392-6481
AD  - Faculty of Medicine, University of Oslo, Norway.
AD  - Department of Cardiology, Oslo University Hospital Rikshospitalet, Norway.
FAU - Arnesen, Harald
AU  - Arnesen H
AUID- ORCID: 0000-0002-0409-8792
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
AD  - Faculty of Medicine, University of Oslo, Norway.
FAU - Helseth, Ragnhild
AU  - Helseth R
AUID- ORCID: 0000-0001-5012-9214
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
AD  - Department of Cardiology, Oslo University Hospital Ulleval, Norway.
FAU - Seljeflot, Ingebjorg
AU  - Seljeflot I
AUID- ORCID: 0000-0003-4071-3358
AD  - Center for Clinical Heart Research, Oslo University Hospital Ulleval, Norway.
AD  - Department of Cardiology, Oslo University Hospital Ulleval, Norway.
AD  - Faculty of Medicine, University of Oslo, Norway.
LA  - eng
SI  - ClinicalTrials.gov/NCT02746822
PT  - Journal Article
DEP - 20210527
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Glycoproteins)
RN  - 0 (IL18 protein, human)
RN  - 0 (IL1B protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (IL6R protein, human)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (glycoprotein 130, human)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Caspase 1/blood
MH  - Coronary Vessels/*pathology
MH  - Cross-Sectional Studies
MH  - Female
MH  - *Gene Expression Profiling
MH  - Glycoproteins/blood
MH  - Humans
MH  - *Inflammasomes
MH  - Inflammation
MH  - Interleukin-18/blood
MH  - Interleukin-1beta/blood
MH  - Interleukin-6/blood/*metabolism
MH  - Leukocytes/metabolism
MH  - Male
MH  - Middle Aged
MH  - Myocardium/*pathology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/blood/*metabolism
MH  - Receptors, Interleukin-6/blood
MH  - ST Elevation Myocardial Infarction/*metabolism
MH  - Signal Transduction
MH  - Thrombosis/*pathology
MH  - Toll-Like Receptor 4/blood
MH  - Young Adult
PMC - PMC8178014
COIS- The authors declare that there is no conflict of interest regarding the 
      publication of this paper.
EDAT- 2021/06/18 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/05/27
CRDT- 2021/06/17 06:39
PHST- 2021/02/18 00:00 [received]
PHST- 2021/04/07 00:00 [revised]
PHST- 2021/05/07 00:00 [accepted]
PHST- 2021/06/17 06:39 [entrez]
PHST- 2021/06/18 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/05/27 00:00 [pmc-release]
AID - 10.1155/2021/5525917 [doi]
PST - epublish
SO  - Mediators Inflamm. 2021 May 27;2021:5525917. doi: 10.1155/2021/5525917. 
      eCollection 2021.